CN113476742A

CN113476742A - System for inhibiting pathological cell division and control method thereof

Info

Publication number: CN113476742A
Application number: CN202110910071.5A
Authority: CN
Inventors: 衷兴华; 汪龙; 杨克; 陶银炯
Original assignee: Hangzhou Vena Anke Medical Technology Co Ltd
Current assignee: Hangzhou Vena Anke Medical Technology Co ltd
Priority date: 2021-08-09
Filing date: 2021-08-09
Publication date: 2021-10-08

Abstract

The embodiment of the application provides a system for inhibiting division of diseased cells and a control method thereof. The system for inhibiting division of diseased cells comprises: electric field generating means for outputting a target electric field to the target tissue to inhibit mitosis of at least a portion of target cells in the target tissue and to cause reversible electroporation of cell membranes of at least a portion of the target cells in the target tissue; the drug-loaded conductive particles are used for carrying the anti-tumor drug and releasing the anti-tumor drug to target tissues, and at least part of the drug-loaded conductive particles enter target cells through reversible electroporation to release the anti-tumor drug. The embodiment of the application realizes the pathological cell treatment mode combining the electric field effect and the medicament effect, is favorable for improving the killing rate of tumor cells, and further improves the treatment effect.

Description

System for inhibiting pathological cell division and control method thereof

Technical Field

The application relates to the technical field of medical equipment, in particular to a system for inhibiting pathological cell division and a control method thereof.

Background

Tumors, especially malignant tumors, are the result of uncontrolled growth of cells relative to normal tissues. The rapid growth of tumors is often the result of relatively frequent cell division or replication of tumor cells relative to healthy cells. Such rapid growth allows the tumor to occupy a growing volume and damage or destroy its adjacent tissues.

In the existing tumor treatment process, electric field therapy with better targeting property is promoted to replace the traditional radiotherapy and/or chemotherapy. However, only the electric field therapy may result in a low killing rate of tumor cells.

Disclosure of Invention

The present application provides a system for inhibiting pathological cell division, a control method thereof, an apparatus, an electronic device and a storage medium, aiming at the disadvantages of the existing methods, so as to solve the technical problem that the killing rate of tumor cells is low by only adopting electric field therapy in the prior art.

In a first aspect, the present embodiments provide a system for inhibiting pathological cell division, comprising:

electric field generating means for outputting a target electric field to the target tissue to inhibit mitosis of at least a portion of target cells in the target tissue and to cause reversible electroporation of cell membranes of at least a portion of the target cells in the target tissue;

the drug-loaded conductive particles are used for carrying the anti-tumor drug and releasing the anti-tumor drug to target tissues, and at least part of the drug-loaded conductive particles enter target cells through reversible electroporation to release the anti-tumor drug.

In one embodiment, the electric field generating device includes: a voltage generator, a voltage controller and at least one pair of electrode patches;

the at least one pair of electrode patches are used for being attached to the surface of the biological tissue corresponding to the target tissue;

the voltage generator is electrically connected with at least one pair of electrode patches and is used for outputting voltage to each electrode patch;

the voltage controller is respectively electrically connected with the voltage generator and the at least one pair of electrode patches and is used for controlling the voltage so as to adjust the electric field intensity and/or direction of the at least one pair of electrode patches, so that each pair of electrode patches forms a target electric field at least surrounding the target tissue.

In one embodiment, the electric field strength of the target electric field is not less than 0.1 volts per centimeter and not more than 10 volts per centimeter.

In one embodiment, the frequency of the target electric field is not less than 50 kilohertz and not greater than 500 kilohertz.

In one embodiment, the voltage generator comprises at least one of a pulse voltage generator and an alternating voltage generator.

Target pulsed electric field the target alternating electric field in one embodiment, each pair of electrode patches is for attachment to opposite sides of a biological tissue surface; the connecting line of any pair of electrode patches and the connecting line of the adjacent pair of electrode patches form an alpha angle, and alpha is more than 0 and less than 90 degrees.

In one embodiment, the drug-loaded conductive particles comprise: conductive particles and an anti-tumor agent carried by the conductive particles;

the antitumor agent comprises one or more of adriamycin, cisplatin, temozolomide, bleomycin and carboplatin.

In one embodiment, the drug-loaded conductive particles comprise particles prepared by the following preparation method:

mixing folic acid with an ethanol solution of a conductive polymer monomer to obtain a first mixed solution;

mixing the first mixed solution with an ammonium persulfate solution to obtain a first precipitate;

cleaning and drying the first precipitate to obtain conductive particles;

and soaking the conductive particles in an anti-tumor agent to obtain the drug-loaded conductive particles.

In one embodiment, folic acid is mixed with an ethanol solution of a conductive polymer monomer to obtain a first mixed solution, including:

dissolving folic acid of not less than 0.05 g and not more than 1 g in deionized water of not less than 100 ml and not more than 120 ml to obtain folic acid solution;

adding the folic acid solution into not less than 2 ml and not more than 3 ml of conductive polymer monomer ethanol solution with the mass concentration of not less than 45% and not more than 50%, and intensively stirring for not less than 30 minutes and not more than 40 minutes to obtain a first mixed solution.

In one embodiment, after mixing the first mixed solution with the ammonium persulfate solution, a first precipitate is obtained, which comprises:

dissolving not less than 8 g and not more than 9 g of ammonium persulfate in not less than 20 ml and not more than 25 ml of deionized water to obtain an ammonium persulfate solution;

uniformly dripping the ammonium persulfate solution into the first mixed solution at room temperature to obtain a second mixed solution, finishing dripping within 1 hour, and then continuously stirring for not less than 2 hours and not more than 3 hours;

after the second mixed solution was allowed to stand overnight, a first precipitate was obtained.

In one embodiment, after the first precipitate is washed and dried, the conductive particles are obtained, and the method comprises the following steps:

washing the first precipitate with deionized water and acetone for 3 times;

and (3) placing the first precipitate in vacuum drying at a temperature of not less than 60 ℃ and not more than 70 ℃ to obtain the conductive particles.

In one embodiment, the conductive particles are soaked in an anti-tumor drug to obtain drug-loaded conductive particles, which includes:

dissolving the anti-tumor drug in a solvent to obtain the anti-tumor drug with the concentration of not less than 100 micrograms per milliliter and not more than 120 micrograms per milliliter;

soaking the conductive particles into an anti-tumor medicament to obtain a third mixed solution, enabling the concentration of the conductive particles in the third mixed solution to be not less than 500 micrograms per milliliter and not more than 550 micrograms per milliliter, and stirring for 24 hours;

centrifuging the third mixed solution at 5000 revolutions per minute to obtain a second precipitate;

and drying the second precipitate in vacuum at room temperature to obtain the drug-loaded conductive particles.

In a second aspect, the present embodiments provide a control method for inhibiting a diseased cell division system based on the first aspect, including:

the electric field generating device in the system for inhibiting the division of the pathological cells is controlled to output a target electric field to the target tissue so as to inhibit the mitosis of at least part of target cells in the target tissue and enable cell membranes of at least part of target cells in the target tissue to form reversible electroporation, so that the drug-carrying conductive particles in the system for inhibiting the division of the pathological cells carry an anti-tumor agent and release the anti-tumor agent to the target tissue, and at least part of the drug-carrying conductive particles enter the target cells through the reversible electroporation to release the anti-tumor agent.

In one embodiment, controlling an electric field generating device in a system for inhibiting division of diseased cells to output a target electric field to a target tissue includes:

and controlling a voltage generator in the electric field generating device to output a target electric field to the target tissue through at least one pair of electrode patches, wherein the electric field intensity of the target electric field is not less than 5 volts per centimeter and not more than 10 volts per centimeter.

controlling a voltage generator in the electric field generating device to output a target electric field to the target tissue through at least one pair of electrode patches, the target electric field having a frequency of not less than 50 kHz and not more than 500 kHz.

In one embodiment, controlling a voltage generator in an electric field generating device to output a target electric field to a target tissue through at least one pair of electrode patches includes:

a pulse voltage generator in the control voltage generator outputs a target pulse electric field to target tissues through at least one pair of electrode patches; and/or, controlling an alternating voltage generator in the voltage generator to output a target alternating electric field to the target tissue through the at least one pair of electrode patches.

and controlling a voltage generator in the electric field generating device to sequentially output a target electric field to the target tissue through each pair of electrode patches at a first time interval.

In a third aspect, the present embodiments provide a control device for inhibiting a diseased cell division system, including:

the control module is used for controlling the electric field generating device in the system for inhibiting the division of the pathological cells to output a target electric field to the target tissue so as to inhibit the mitosis of at least part of target cells in the target tissue and enable cell membranes of at least part of target cells in the target tissue to form reversible electroporation, so that the drug-carrying conductive particles in the system for inhibiting the division of the pathological cells carry an anti-tumor drug and release the anti-tumor drug to the target tissue, and at least part of the drug-carrying conductive particles enter the target cells through the reversible electroporation to release the anti-tumor drug.

In a fourth aspect, an embodiment of the present application provides an electronic device, including:

a processor;

a memory electrically connected to the processor;

at least one program stored in the memory and configured to be executed by the processor, the at least one program configured to: the control method for inhibiting the division system of the diseased cells as provided in the second aspect is realized.

In a fifth aspect, the present embodiments provide a computer-readable storage medium, on which a computer program is stored, where the computer program, when executed by an electronic device, implements the control method for inhibiting a diseased cell division system according to the second aspect.

The beneficial technical effects brought by the technical scheme provided by the embodiment of the application comprise: the pathological cell treatment mode combining the electric field effect and the medicament effect can be realized, the killing rate of tumor cells is favorably improved, and the treatment effect is further improved.

Specifically, the target electric field is output to the target tissue through the electric field generating device, on one hand, organelles in cells which are dividing can be inhibited from moving towards two poles, and even the organelles can be pulled towards an equatorial plate to induce the cells to be collapsed or broken, so that the effect of inhibiting the cells from being divided or destroying the cells is achieved, the target electric field hardly influences the cells which are not divided, the distinguishing capability of the tumor cells and the healthy cells is improved, the treatment effect can be improved, and the side effect can be greatly reduced; on the other hand, reversible electroporation can be formed on cell membranes of at least part of target cells in the target tissue, so that the permeability of the part of target cells is increased, and favorable conditions are created for releasing the anti-tumor agent by allowing at least part of drug-loaded conductive particles to enter the target cells;

the drug-loaded conductive particles can release the carried anti-tumor drug to target tissues, so that the treatment effect is improved; under the action of an electric field formed by a target electric field output to a target tissue by the electric field generating device, the targeting property of the migration of the drug-loaded conductive particles is improved, and the utilization rate of the anti-tumor agent is improved; at least part of the drug-carrying conductive particles can enter target cells by utilizing reversible electroporation formed by cell membranes to release an anti-tumor drug, so that the treatment effect is further improved.

Additional aspects and advantages of the present application will be set forth in part in the description which follows and, in part, will be obvious from the description, or may be learned by practice of the present application.

Drawings

The foregoing and/or additional aspects and advantages of the present application will become apparent and readily appreciated from the following description of the embodiments, taken in conjunction with the accompanying drawings of which:

FIG. 1 is a schematic diagram of a structural framework of a system for inhibiting division of diseased cells according to an embodiment of the present application;

FIG. 2 is a schematic structural framework diagram of an electric field generating device in a system for inhibiting division of diseased cells according to an embodiment of the present application;

fig. 3 is a schematic structural framework diagram of an electronic device according to an embodiment of the present application.

In the figure:

100-inhibition of the diseased cell division system;

110-electric field generating means; 111-a voltage generator; 112-electrode patch; 113-a voltage controller;

120-drug-loaded conductive particles;

200-an electronic device; 210-a memory; 220-a processor; 230-a bus; 240-a monitoring unit; 250-a transceiver; 260-an input unit; 270-output unit.

Detailed Description

Reference will now be made in detail to the present application, examples of which are illustrated in the accompanying drawings, wherein like reference numerals refer to the same or similar parts or parts having the same or similar functions throughout. In addition, if a detailed description of the known art is not necessary for illustrating the features of the present application, it is omitted. The embodiments described below with reference to the drawings are exemplary only for the purpose of explaining the present application and are not to be construed as limiting the present application.

It will be understood by those within the art that, unless otherwise defined, all terms (including technical and scientific terms) used herein have the same meaning as commonly understood by one of ordinary skill in the art to which this application belongs. It will be further understood that terms, such as those defined in commonly used dictionaries, should be interpreted as having a meaning that is consistent with their meaning in the context of the prior art and will not be interpreted in an idealized or overly formal sense unless expressly so defined herein.

As used herein, the singular forms "a", "an", "the" and "the" are intended to include the plural forms as well, unless the context clearly indicates otherwise. It will be further understood that the terms "comprises" and/or "comprising," when used in this specification, specify the presence of stated features, integers, steps, operations, elements, and/or components, but do not preclude the presence or addition of one or more other features, integers, steps, operations, elements, components, and/or groups thereof. It will be understood that when an element is referred to as being "connected" or "coupled" to another element, it can be directly connected or coupled to the other element or intervening elements may also be present. Further, "connected" or "coupled" as used herein may include wirelessly connected or wirelessly coupled. As used herein, the term "and/or" includes all or any element and all combinations of one or more of the associated listed items.

The inventors of the present application have conducted research and found that electric field therapy has better targeting properties and fewer side effects than conventional tumor treatments such as radiotherapy and/or chemotherapy. However, only the electric field therapy may result in a low killing rate of tumor cells.

In the device for destroying diseased cells or inhibiting the division of diseased cells, electrode patches can be adopted, electric fields are alternately generated on each pair of electrode patches to inhibit the mitosis of tumor cells, and the tumor tissue cells in the edge area of a target area are difficult to inhibit the mitosis due to the attenuation of the electric fields. Also, the direction of the electric field is fixed, and some target tissue regions of the biological tissue may not be covered to the target electric field, thereby limiting the therapeutic effect.

The inventor of the application considers that the electric field is adopted to inhibit or kill the division of pathological cells, and the medicament is matched to act so as to improve the treatment effect. However, if the anti-tumor agent is simply injected into the target tissue, the anti-tumor agent is diffused disorderly, which affects the therapeutic effect, the utilization rate of the anti-tumor agent is low, and the anti-tumor agent easily accidentally damages healthy tissue cells around the target tissue and causes side effects.

The present application provides a system for inhibiting pathological cell division, a method and an apparatus for controlling the same, an electronic device and a storage medium, which are intended to solve the above technical problems of the prior art.

The following describes the technical solutions of the present application and how to solve the above technical problems with specific embodiments.

The embodiment of the present application provides a system 100 for inhibiting pathological cell division, and a schematic structural diagram of the system 100 for inhibiting pathological cell division is shown in fig. 1, including: an electric field generating device 110 and drug-loaded conductive particles 120.

The electric field generating device 110 is used for outputting a target electric field to the target tissue to inhibit mitosis of at least part of target cells in the target tissue and enable reversible electroporation of cell membranes of at least part of target cells in the target tissue.

The drug-loaded conductive particles 120 are used for carrying and releasing the anti-tumor drug to target tissues, and at least part of the drug-loaded conductive particles 120 enter target cells through reversible electroporation to release the anti-tumor drug.

The pathological cell division inhibiting system 100 provided by this embodiment can realize a pathological cell treatment mode combining an electric field effect and a medicament effect, and is beneficial to improving the killing rate of tumor cells, thereby improving the treatment effect.

Specifically, the electric field generating device 110 outputs the target electric field to the target tissue (i.e., focal tissue), so that on one hand, organelles in dividing cells can be inhibited from moving towards two poles, and even the organelles can be pulled towards an equatorial plate, so as to induce the cells to be collapsed or broken, and the effect of inhibiting the cells from being divided or destroying the cells can be achieved, and the target electric field hardly influences the cells which are not divided, so that the capability of distinguishing tumor cells from healthy cells can be improved, the treatment effect can be improved, and the side effect can be greatly reduced; on the other hand, reversible electroporation can be formed on cell membranes of at least part of target cells in the target tissue, so that the permeability of the part of target cells is increased, and favorable conditions are created for releasing the anti-tumor agent by allowing at least part of the drug-loaded conductive particles 120 to enter the target cells.

The drug-loaded conductive particles 120 can release the carried antitumor drug to target tissues, so that the treatment effect is improved; under the action of an electric field formed by a target electric field output to a target tissue by the electric field generating device 110, the targeting property of the migration of the drug-loaded conductive particles 120 is improved, and the utilization rate of the anti-tumor agent is improved; at least part of the drug-loaded conductive particles 120 can enter target cells by utilizing reversible electroporation formed by cell membranes to release an anti-tumor drug, so that the treatment effect is further improved.

The action mechanism of the antitumor agent mainly comprises: inhibition of DNA or RNA synthesis (against nucleic acid synthesis species such as cytarabine); rendering the DNA non-functional by cross-linking (e.g., alkylating agents); inhibit the DNA enzyme related to maintaining the three-dimensional structure, and influence the replication, transcription, repair, recombination, etc. of DNA (such as anthracyclines, podophyllum drugs, etc.). The tumor cell sensitive antitumor medicine can induce tumor cell apoptosis through up regulating apoptosis promoting gene (such as p53) and down regulating apoptosis inhibiting gene (such as Myc, Bcl-2, etc.).

In some embodiments, the system for inhibiting division of diseased cells 100 may further comprise an upper computer. The upper computer is in communication connection with the electric field generating device 110.

In this embodiment, the upper computer may implement program update or data backup in the electric field generation device 110, and may also implement remote control on the electric field generation device 110, thereby facilitating function expansion of the electric field generation device 110.

In one example, the host computer is communicatively connected to the electric field generating device 110 via WIFI (Wireless Fidelity).

In one example, the upper computer is communicatively connected to the electric field generating device 110 through the cloud.

The inventors of the present application consider that the electric field generating device 110 needs to output a target electric field to a target tissue. To this end, the present application provides one possible implementation manner for the electric field generating device 110:

as shown in fig. 2, the electric field generating apparatus 110 according to the embodiment of the present application includes: a voltage generator 111, a voltage controller 113, and at least one pair of electrode patches 112.

At least one pair of electrode patches 112 is adapted to be attached to a biological tissue surface corresponding to a target tissue.

The voltage generator 111 is electrically connected to at least one pair of electrode patches 112, and outputs a voltage to each of the electrode patches 112.

The voltage controller 113 is electrically connected to the voltage generator 111 and the at least one pair of electrode patches 112, respectively, for controlling the voltage to adjust the electric field strength and/or direction of the at least one pair of electrode patches 112 such that each pair of electrode patches 112 forms a target electric field at least surrounding the target tissue.

In the present embodiment, the voltage generator 111 is used to generate an initial voltage, and the voltage controller 113 controls and transmits the voltage output by the voltage generator 111 to the electrode patch 112, so that the electrode patch 112 can apply a target electric field to the target tissue, and the target electric field can apply a potential to the target cell to induce an electric field in the target cell.

For the dividing cells, on one hand, electric field lines induced in the cells are gathered at the equatorial plate, and the organelles are subjected to electric field force directed to the equatorial plate, namely, the electric field force can limit the organelles to move towards two poles, so that certain inhibiting effect on cell division can be achieved.

On the other hand, as the degree of cell division increases (i.e., the equatorial plate narrows), the electric field lines at the equatorial plate become denser, and the increased electric field force can pull the organelles toward the equatorial plate, thus hindering the formation of the cell plate, and further inhibiting cell division, even inducing cell rupture or apoptosis.

On the other hand, the cellular organelles are gathered at the equatorial plate, which causes an increase in the pressure near the equatorial plate, which may rupture the cell membrane, especially in the state of narrowing of the equatorial plate. And the target electric field can make the organelle subject to pulse type electric field force, namely the organelle has certain hammering effect, thus the possibility of rupture of the cell membrane can be improved. In addition, the pulsed electric field force applied to the organelles also affects the structures of the organelles, and can induce the disintegration or the rupture of the organelles and further induce the cell rupture or the apoptosis.

On the other hand, the target electric field can make the cell membrane of at least part of target cells in the target tissue form reversible electroporation, so that the permeability of the part of target cells is increased, and favorable conditions are created for the at least part of the drug-loaded conductive particles 120 to enter the target cells to release the anti-tumor drug.

In some embodiments, the electric field strength of the target electric field is not less than 0.1 volts per centimeter and not greater than 10 volts per centimeter. Under the electric field intensity, the mitosis of at least part of target cells in the target tissue is inhibited, and reversible electroporation is formed on cell membranes of at least part of target cells in the target tissue.

In some embodiments, the frequency of the target electric field is not less than 50 khz and not greater than 500 khz. Under the frequency of the electric field, the damage to the pathological cells or the inhibition of the division of the pathological cells can be realized.

In some embodiments, the voltage generator 111 comprises at least one of a pulse voltage generator and an alternating voltage generator. That is, the voltage generator 111 may include a pulse voltage generator that generates only a target pulse electric field; the voltage generator 111 may also include an alternating voltage generator that generates only the target alternating electric field; the voltage generator 111 may further include a pulse voltage generator and an alternating voltage generator, and may generate both a target pulse electric field and a target alternating electric field.

The present inventors consider that the electrode patch 112 is the terminal for outputting the target electric field to the target tissue, and the manner of use of the electrode patch 112 will determine the electric field pattern obtained by the target tissue. To this end, the present application provides one possible implementation for the electrode patch 112 as follows:

each pair of electrode patches of the embodiments of the present application is adapted to be affixed to opposite sides of a biological tissue surface. The connecting line of any pair of electrode patches and the connecting line of the adjacent pair of electrode patches form an alpha angle, and alpha is more than 0 and less than 90 degrees.

In the present embodiment, the voltage generator 111 may apply an anisotropic voltage to each pair of electrode patches 112 so that a target electric field is formed between each pair of electrode patches 112. The number of the electrode patches 112 is 2 pairs or more, which is beneficial to forming a composite electric field and strengthening the effect of the electric field.

It should be noted that the electric field intensity in the vicinity of the connecting line between each pair of electrode patches 112 is optimized, and this electric field intensity is generally mainly used. Therefore, in this embodiment, the connecting line of the two adjacent pairs of electrode patches 112 forms an acute angle, which is beneficial for the electric fields generated by the two adjacent pairs of electrode patches 112 to be mutually superimposed to form a composite electric field.

The inventors of the present application consider that the drug-loaded conductive particles 120 need to carry and release the anti-tumor agent to the target tissue, and at least part of the drug-loaded conductive particles 120 enter the target cells through reversible electroporation to release the anti-tumor agent. For this reason, the present application provides one possible implementation manner for the drug-loaded conductive particles 120 as follows:

the drug-loaded conductive particles 120 of the embodiments of the present application include: conductive particles and an antitumor agent carried by the conductive particles.

In this embodiment, the conductive particles are used as carriers of an antitumor agent, and are favorable for migration under the action of an electric field, so that the migration targeting property is improved.

In some embodiments, the drug-loaded conductive particles 120 have a nanoscale particle size that facilitates release of the anti-tumor agent into target cells via reversible electroporation of cellular membrane formation.

The inventors of the present application provide a preparation method for obtaining the aforementioned drug-loaded conductive particles 120, comprising steps S101-S104:

s101: mixing folic acid and an ethanol solution of a conductive polymer monomer to obtain a first mixed solution.

S102: and mixing the first mixed solution with an ammonium persulfate solution to obtain a first precipitate.

S103: and cleaning and drying the first precipitate to obtain the conductive particles.

S104: and soaking the conductive particles in an anti-tumor agent to obtain the drug-loaded conductive particles.

The inventor of the present application further provides a development method of the preparation method for obtaining the aforementioned drug-loaded conductive particles, comprising steps S201 to S211:

s201: dissolving folic acid of not less than 0.05 g and not more than 1 g in deionized water of not less than 100 ml and not more than 120 ml to obtain folic acid solution.

S202: adding the folic acid solution into not less than 2 ml and not more than 3 ml of conductive polymer monomer ethanol solution with the mass concentration of not less than 45% and not more than 50%, and intensively stirring for not less than 30 minutes and not more than 40 minutes to obtain a first mixed solution.

In step S202, the conductive polymer monomer may be pyrrole or aniline.

S203: dissolving not less than 8 g and not more than 9 g of ammonium persulfate in not less than 20 ml and not more than 25 ml of deionized water to obtain an ammonium persulfate solution.

S204: and (3) uniformly dropwise adding the ammonium persulfate solution into the first mixed solution at room temperature to obtain a second mixed solution, finishing dropwise adding for 1 hour, and then continuously stirring for not less than 2 hours and not more than 3 hours.

S205: after the second mixed solution was allowed to stand overnight, a first precipitate was obtained.

S206: the first precipitate was washed 3 times with deionized water and acetone, respectively.

S207: and (3) placing the first precipitate in vacuum drying at a temperature of not less than 60 ℃ and not more than 70 ℃ to obtain the conductive particles.

After step S207, the particle diameter of the obtained conductive particle may be not less than 60 nm and not more than 100 nm.

S208: dissolving the anti-tumor drug in a solvent to obtain the anti-tumor drug at a concentration of not less than 100 micrograms per milliliter and not more than 120 micrograms per milliliter.

In step S208, the anti-tumor drug may be any one of doxorubicin, cisplatin, temozolomide, bleomycin, and carboplatin.

S209: and soaking the conductive particles into the anti-tumor medicament to obtain a third mixed solution, enabling the concentration of the conductive particles in the third mixed solution to be not less than 500 micrograms per milliliter and not more than 550 micrograms per milliliter, and stirring for 24 hours.

After step S209, the antitumor agent may be attached to the surface of the conductive particles and enter the pores of the conductive particles.

S210: the third mixed solution was centrifuged at 5000 rpm to obtain a second precipitate.

S211: and drying the second precipitate in vacuum at room temperature to obtain the drug-loaded conductive particles 120.

Based on the same inventive concept, the present application provides a control method of any one of the systems 100 for inhibiting division of diseased cells, which includes:

the electric field generating device 110 in the system 100 for inhibiting pathological cell division is controlled to output a target electric field to a target tissue so as to inhibit mitosis of at least part of target cells in the target tissue, and reversible electroporation is formed on cell membranes of at least part of target cells in the target tissue, so that the drug-carrying conductive particles 120 in the system 100 for inhibiting pathological cell division carry an anti-tumor drug and release the anti-tumor drug to the target tissue, and at least part of the drug-carrying conductive particles 120 enter the target cells through the reversible electroporation to release the anti-tumor drug.

In this embodiment, by controlling the electric field generating device 110 to output the target electric field to the target tissue (i.e., the focal tissue), on one hand, the organelles in the dividing cells can be inhibited from moving towards two poles, and even the organelles can be pulled towards the equatorial plate, so as to induce the cells to be disrupted or broken, thereby achieving the effect of inhibiting the cells from being divided or destroying the cells, and the target electric field hardly affects the cells which are not divided, thereby improving the capability of distinguishing the tumor cells from the healthy cells, not only improving the treatment effect, but also greatly reducing the side effects; on the other hand, reversible electroporation can be formed on cell membranes of at least part of target cells in the target tissue, so that the permeability of the part of target cells is increased, and favorable conditions are created for releasing the anti-tumor agent by allowing at least part of the drug-loaded conductive particles 120 to enter the target cells.

The electric field formed by controlling the target electric field output by the electric field generating device 110 to the target tissue can guide and inhibit the ordered movement of the drug-loaded conductive particles 120 in the lesion cell division system 100 in the target tissue, which is beneficial to improving the targeting property of the migration of the drug-loaded conductive particles 120 and improving the utilization rate of the antitumor agent; at least part of the drug-loaded conductive particles 120 can enter target cells by utilizing reversible electroporation formed by cell membranes to release an anti-tumor drug, so that the treatment effect is further improved.

It is understood that the drug-loaded particles can be injected into the target tissue before controlling the electric field generating device 110 in the system 100 for inhibiting pathological cell division to output the target electric field to the target tissue. The drug-loaded particles can also be injected into the target tissue while controlling the electric field generating device 110 in the system 100 for inhibiting the division of diseased cells to output the target electric field to the target tissue.

In some embodiments, controlling the electric field generating device 110 in the system 100 for inhibiting division of diseased cells to output a target electric field to a target tissue includes: the voltage generator 111 in the electric field generating device 110 is controlled to output a target electric field, which has an electric field strength of not less than 5 volts per centimeter and not more than 10 volts per centimeter, to the target tissue through the at least one pair of electrode patches 112.

At the electric field intensity provided by the present embodiment, it is advantageous to achieve the goal of inhibiting the mitosis of at least a portion of the target cells in the target tissue and allowing the cell membrane of at least a portion of the target cells in the target tissue to form reversible electroporation.

In one example, the electrode patch 112 may be manually or robotically attached to a biological tissue surface corresponding to a target tissue before implementing the control method provided by the present embodiment.

In some embodiments, controlling the electric field generating device 110 in the system 100 for inhibiting division of diseased cells to output a target electric field to a target tissue includes: the voltage generator 111 in the electric field generating device 110 is controlled to output a target electric field, having a frequency of not less than 50 khz and not more than 500 khz, to the target tissue through the at least one pair of electrode patches 112.

In some embodiments, controlling a voltage generator in the electric field generating device to output a target electric field to a target tissue through at least one pair of electrode patches includes: a pulse voltage generator in the control voltage generator outputs a target pulse electric field to target tissues through at least one pair of electrode patches; and/or, controlling an alternating voltage generator in the voltage generator to output a target alternating electric field to the target tissue through the at least one pair of electrode patches.

In one example, the electrode patches 112 in the electric field generating device 110 include 2 pairs, wherein one pair of electrode patches 112 is electrically connected to a pulse voltage generator and the other pair of electrode patches 112 is electrically connected to an alternating voltage generator. The pulse voltage generator and the alternating voltage generator can output corresponding voltages at the same time to form a composite electric field, so that the effect of the electric field is enhanced.

In some embodiments, controlling the voltage generator 111 in the electric field generating device 110 to output a target electric field to the target tissue through at least one pair of electrode patches 112 includes: at a first time interval, the voltage generator 111 in the electric field generating device 110 is controlled to output a target electric field to the target tissue through each pair of electrode patches 112 in turn.

In one example, the electrode patches 112 in the electric field generating device 110 include 2 pairs, and the connecting line of two adjacent pairs of electrode patches 112 forms an acute angle, and each pair of electrode patches 112 is controlled to sequentially output a target electric field to a target tissue at a first time interval, so as to alternately generate electric fields, which is beneficial to form a rotating electric field in the target tissue region.

Based on the same inventive concept, the embodiment of the present application provides a control device for inhibiting a diseased cell division system, which includes:

the control module is configured to control the electric field generating device 110 in the system 100 for inhibiting pathological cell division to output a target electric field to a target tissue, so as to inhibit mitosis of at least part of target cells in the target tissue, and enable cell membranes of at least part of target cells in the target tissue to form reversible electroporation, so that the drug-loaded conductive particles 120 in the system 100 for inhibiting pathological cell division carry an anti-tumor drug and release the anti-tumor drug to the target tissue, and at least part of the drug-loaded conductive particles 120 enter the target cells through the reversible electroporation to release the anti-tumor drug.

In some embodiments, the control module is further to: the voltage generator 111 in the electric field generating device 110 is controlled to output a target electric field, which has an electric field strength of not less than 5 volts per centimeter and not more than 10 volts per centimeter, to the target tissue through the electrode patch 112.

In some embodiments, the control module is further to: the voltage generator 111 in the electric field generating device 110 is controlled to output a target electric field, having a frequency of not less than 50 khz and not more than 500 khz, to the target tissue through the at least one pair of electrode patches 112.

In some embodiments, the control module is further to: a pulse voltage generator in the control voltage generator outputs a target pulse electric field to target tissues through at least one pair of electrode patches; and/or, controlling an alternating voltage generator in the voltage generator to output a target alternating electric field to the target tissue through the at least one pair of electrode patches.

In some embodiments, the control module is further to: at a first time interval, the voltage generator 111 in the electric field generating device 110 is controlled to output a target electric field to the target tissue through each pair of electrode patches 112 in turn.

The control device for the system 100 for inhibiting pathological cell division provided in this embodiment can execute any control method for inhibiting pathological cell division 100 provided in this embodiment, which is similar to the principle and is not described herein again.

Based on the same inventive concept, an embodiment of the present application provides an electronic device 200, where a schematic structural framework of the electronic device 200 is shown in fig. 3, and the electronic device includes: a memory 210 and a processor 220.

The memory 210 is electrically connected to the processor 220.

At least one computer program stored in the memory 210 and configured to be executed by the processor 220, the at least one program configured to: implementing any of the control methods of the system 100 for inhibiting division of diseased cells as provided in the previous embodiments.

In the present embodiment, processor 220 and memory 210 are electrically coupled, such as by bus 230. Alternatively, the Processor 220 may be a CPU (Central Processing Unit), a general-purpose Processor, a DSP (Digital Signal Processor), an ASIC (Application Specific Integrated Circuit), an FPGA (Field-Programmable Gate Array), or other Programmable logic device, a transistor logic device, a hardware component, or any combination thereof. The processor 220 may implement or execute the various illustrative logical blocks, modules, and circuits described in connection with the disclosure herein. Processor 220 may also be a combination of computing functions, e.g., comprising one or more microprocessors, a combination of a DSP and a microprocessor, or the like.

Alternatively, bus 230 may include a path that transfers information between the aforementioned components. The bus 230 may be a PCI (Peripheral Component Interconnect) bus, an EISA (Extended Industry Standard Architecture) bus, or the like. The bus 230 may be divided into an address bus, a data bus, a control bus, and the like.

Alternatively, Memory 210 may be, but is not limited to, a ROM (Read-Only Memory) or other type of static storage device that can store static information and instructions, a RAM (random access Memory) or other type of dynamic storage device that can store information and instructions, an EEPROM (Electrically Erasable Programmable Read Only Memory), a CD-ROM (Compact Disc Read-Only Memory) or other optical Disc storage, optical Disc storage (including Compact Disc, laser Disc, optical Disc, digital versatile Disc, blu-ray Disc, etc.), a magnetic disk storage medium or other magnetic storage device, or any other medium that can be used to carry or store desired program code in the form of instructions or data structures and that can be accessed by a computer.

In some embodiments, the electronic device 200 may further include a monitoring unit 240. The monitoring unit 240 may be configured to monitor current and/or voltage parameters of the electrode patch 112, and the processor 220 determines the operating state of the electrode patch 112 through the current and/or voltage parameters of the electrode patch 112 obtained by the monitoring unit 240. For example, if the current and/or voltage parameters of the electrode patch 112 obtained by the monitoring unit 240 correspond to the current and/or voltage of the electrode patch 112 when the electrode patch is empty (not connected to a load), it is determined that the electrode patch 112 has currently outputted the target electric field.

In some embodiments, the electronic device 200 may also include a transceiver 250. The transceiver 250 may be used for reception and transmission of signals. The transceiver 250 may allow the processor 220 of the electronic device 200 to perform wireless or wired communication with other devices to exchange data, for example, when the processor 220 receives an instruction to stop outputting the target electric field from a user through the transceiver 250, the processor 220 is triggered to control the voltage generator 111 to start outputting the voltage or control the voltage generator 111 to stop outputting the voltage. It should be noted that the transceiver 250 is not limited to one in practical applications.

In some embodiments, the electronic device 200 may further include an input unit 260. The input unit 260 may be used to receive input numeric, character, image and/or sound information or to generate key signal inputs related to user settings and function control of the processor 220. The input unit 260 may include, but is not limited to, one or more of a touch screen, a physical keyboard, function keys (such as volume control keys, switch keys, etc.), a trackball, a mouse, a joystick, a camera, a microphone, and the like.

In some embodiments, the electronic device 200 may further include an output unit 270. The output unit 270 may be used to output or present information processed by the processor 220. The output unit 270 may include, but is not limited to, one or more of a display device, a speaker, a vibration device, and the like.

It will be appreciated by those skilled in the art that the processor 220 of the electronic device 200 provided in the embodiments of the present application may be specially designed and manufactured for the required purposes, or may comprise a known device in a general-purpose computer. These devices have stored therein computer programs that are selectively activated or reconfigured. Such a computer program may be stored in a device (e.g., computer) readable medium or in any type of medium suitable for storing electronic instructions and each coupled to bus 230.

Based on the same inventive concept, embodiments of the present application provide a computer-readable storage medium, and when being executed by an electronic device, the computer program implements any one of the control methods for inhibiting a diseased cell division system, as provided in the foregoing embodiments.

The embodiments of the present application provide a computer readable storage medium suitable for various alternative embodiments of the above-mentioned control method for inhibiting a diseased cell division system. And will not be described in detail herein.

Those skilled in the art will appreciate that the computer-readable storage media provided by the embodiments can be any available media that can be accessed by the electronic device and includes both volatile and nonvolatile media, removable and non-removable media. The computer-readable storage medium includes, but is not limited to, any type of disk including floppy disks, hard disks, optical disks, CD-ROMs, and magnetic-optical disks, ROMs, RAMs, EPROMs (Erasable Programmable Read-Only memories), EEPROMs (Electrically Erasable Programmable Read-Only memories), flash memories, magnetic cards, or optical cards. That is, a computer-readable storage medium includes any medium that stores or transmits information in a form readable by a device (e.g., a computer).

By applying the embodiment of the application, at least the following beneficial effects can be realized:

1. the pathological cell treatment mode combining the electric field effect and the medicament effect can be realized, the killing rate of tumor cells is favorably improved, and the treatment effect is further improved.

2. The target electric field is output to the target tissue through the electric field generating device 110, so that organelles in cells which are dividing can be inhibited from moving towards two poles, even the organelles can be pulled towards an equatorial plate, the cells are induced to be disintegrated or broken, the effect of inhibiting the cells from being divided or destroying the cells is achieved, the target electric field hardly influences the cells which are not divided, the distinguishing capability of the tumor cells and the healthy cells is further improved, the treatment effect can be improved, and the side effect can be greatly reduced.

3. The target electric field is output to the target tissue through the electric field generating device 110, so that reversible electroporation can be formed on cell membranes of at least part of target cells in the target tissue, the permeability of the part of target cells is increased, and favorable conditions are created for releasing the anti-tumor agent by allowing at least part of the drug-carrying conductive particles 120 to enter the target cells.

4. The drug-loaded conductive particles 120 can release the carried antitumor drug to target tissues, so that the treatment effect is improved; under the action of an electric field formed by a target electric field output to a target tissue by the electric field generating device 110, the targeting property of the migration of the drug-loaded conductive particles 120 is improved, and the utilization rate of the anti-tumor agent is improved; at least part of the drug-loaded conductive particles 120 can enter target cells by utilizing reversible electroporation formed by cell membranes to release an anti-tumor drug, so that the treatment effect is further improved.

Those of skill in the art will appreciate that the various operations, methods, steps in the processes, acts, or solutions discussed in this application can be interchanged, modified, combined, or eliminated. Further, other steps, measures, or schemes in various operations, methods, or flows that have been discussed in this application can be alternated, altered, rearranged, broken down, combined, or deleted. Further, steps, measures, schemes in the prior art having various operations, methods, procedures disclosed in the present application may also be alternated, modified, rearranged, decomposed, combined, or deleted.

In the description of the present application, it is to be understood that the terms "center", "upper", "lower", "front", "rear", "left", "right", "vertical", "horizontal", "top", "bottom", "inner", "outer", and the like indicate orientations or positional relationships based on those shown in the drawings, and are only for convenience in describing the present application and simplifying the description, but do not indicate or imply that the referred device or element must have a particular orientation, be constructed in a particular orientation, and be operated, and thus should not be construed as limiting the present application.

The terms "first", "second" and "first" are used for descriptive purposes only and are not to be construed as indicating or implying relative importance or implicitly indicating the number of technical features indicated. Thus, a feature defined as "first" or "second" may explicitly or implicitly include one or more of that feature. In the description of the present application, "a plurality" means two or more unless otherwise specified.

In the description of the present application, it is to be noted that, unless otherwise explicitly specified or limited, the terms "mounted," "connected," and "connected" are to be construed broadly, e.g., as meaning either a fixed connection, a removable connection, or an integral connection; they may be connected directly or indirectly through intervening media, or they may be interconnected between two elements. The specific meaning of the above terms in the present application can be understood in a specific case by those of ordinary skill in the art.

In the description herein, particular features, structures, materials, or characteristics may be combined in any suitable manner in any one or more embodiments or examples.

The foregoing is only a partial embodiment of the present application, and it should be noted that, for those skilled in the art, several modifications and decorations can be made without departing from the principle of the present application, and these modifications and decorations should also be regarded as the protection scope of the present application.

Claims

1. A system for inhibiting division of diseased cells, comprising:

electric field generating means for outputting a target electric field to a target tissue to inhibit mitosis of at least some target cells in the target tissue and to cause reversible electroporation of cell membranes of at least some target cells in the target tissue;

the medicine-carrying conductive particles are used for carrying an anti-tumor medicine and releasing the anti-tumor medicine to the target tissue, and at least part of the medicine-carrying conductive particles enter the target cells through the reversible electroporation to release the anti-tumor medicine.

2. The diseased cell division inhibiting system of claim 1, wherein the electric field generating device comprises: a voltage generator, a voltage controller and at least one pair of electrode patches;

at least one pair of the electrode patches is used for being attached to the surface of the biological tissue corresponding to the target tissue;

the voltage generator is electrically connected with at least one pair of the electrode patches and is used for outputting voltage to each electrode patch;

3. The system of claim 2, wherein the electric field strength of the target electric field is not less than 0.1 volts per centimeter and not more than 10 volts per centimeter.

4. The diseased cell division inhibiting system of claim 2 wherein the frequency of the target electric field is no less than 50 kilohertz and no greater than 500 kilohertz.

5. The system of any one of claims 2-4, wherein the voltage generator comprises at least one of a pulsed voltage generator and an alternating voltage generator.

6. The system for inhibiting pathological cell division according to claim 2, wherein each pair of the electrode patches is configured to be attached to opposite sides of the surface of the biological tissue; an angle alpha is formed between the connecting line of any pair of the electrode patches and the connecting line of the adjacent pair of the electrode patches, and alpha is more than 0 and less than 90 degrees.

7. The diseased cell division inhibiting system of claim 1, wherein the drug-loaded conductive particles comprise: conductive particles and an anti-tumor agent carried by the conductive particles;

the anti-tumor agent comprises one or more of adriamycin, cisplatin, temozolomide, bleomycin and carboplatin.

8. The system for inhibiting pathological cell division according to claim 1, wherein the drug-loaded conductive particles comprise particles prepared by the following preparation method:

cleaning and drying the first precipitate to obtain conductive particles;

9. The system for inhibiting pathological cell division according to claim 8, wherein the mixing of folic acid with an ethanol solution of conductive polymer monomer to obtain a first mixed solution comprises:

and adding the folic acid solution into a conductive polymer monomer ethanol solution with the mass concentration of not less than 45% and not more than 50% and not less than 2 ml and not more than 3 ml, and intensively stirring for not less than 30 minutes and not more than 40 minutes to obtain the first mixed solution.

10. The system for inhibiting pathological cell division according to claim 8, wherein the mixing the first mixed solution with the ammonium persulfate solution to obtain the first precipitate comprises:

uniformly dropwise adding the ammonium persulfate solution into the first mixed solution at room temperature to obtain a second mixed solution, after dropwise adding is completed within 1 hour, continuously stirring for not less than 2 hours and not more than 3 hours;

and standing the second mixed solution overnight to obtain the first precipitate.

11. The system for inhibiting pathological cell division according to claim 8, wherein the washing and drying of the first precipitate to obtain conductive particles comprises:

washing the first precipitate respectively with deionized water and acetone for 3 times;

and placing the first precipitate in vacuum drying at a temperature of not less than 60 ℃ and not more than 70 ℃ to obtain the conductive particles.

12. The system for inhibiting pathological cell division according to claim 8, wherein the drug-loaded conductive particles obtained by soaking the conductive particles in an anti-tumor drug comprise:

soaking the conductive particles into the anti-tumor medicament to obtain a third mixed solution, enabling the concentration of the conductive particles in the third mixed solution to be not less than 500 micrograms per milliliter and not more than 550 micrograms per milliliter, and stirring for 24 hours;

13. A control method for inhibiting the division system of diseased cells based on any one of claims 1 to 12, comprising:

controlling an electric field generating device in the system for inhibiting pathological cell division to output a target electric field to a target tissue so as to inhibit mitosis of at least part of target cells in the target tissue and enable cell membranes of at least part of target cells in the target tissue to form reversible electroporation, so that the anti-tumor drug is carried by the drug-carrying conductive particles in the system for inhibiting pathological cell division and released to the target tissue, and at least part of the drug-carrying conductive particles enter the target cells through the reversible electroporation to release the anti-tumor drug.

14. The method according to claim 13, wherein the controlling of the electric field generating device in the lesion cell division suppressing system to output a target electric field to a target tissue comprises:

15. The method according to claim 13, wherein the controlling of the electric field generating device in the lesion cell division suppressing system to output a target electric field to a target tissue comprises:

controlling a voltage generator in the electric field generating device to output a target electric field to a target tissue through at least one pair of electrode patches, the target electric field having a frequency of not less than 50 kilohertz and not more than 500 kilohertz.

16. The method according to claim 14 or 15, wherein the controlling the voltage generator in the electric field generating device to output a target electric field to a target tissue through at least one pair of electrode patches comprises:

controlling a pulse voltage generator in the voltage generators to output a target pulse electric field to target tissues through at least one pair of the electrode patches; and/or controlling an alternating current voltage generator in the voltage generators to output a target alternating current electric field to target tissue through at least one pair of the electrode patches.

17. The method according to claim 14 or 15, wherein the controlling the voltage generator in the electric field generating device to output a target electric field to a target tissue through at least one pair of electrode patches comprises:

18. A control device for inhibiting a diseased cell division system, comprising:

the control module is used for controlling the electric field generating device in the system for inhibiting the division of the pathological cells to output a target electric field to a target tissue so as to inhibit the mitosis of at least part of target cells in the target tissue and enable cell membranes of at least part of target cells in the target tissue to form reversible electroporation, so that the drug-carrying conductive particles in the system for inhibiting the division of the pathological cells carry an anti-tumor drug and release the anti-tumor drug to the target tissue, and at least part of the drug-carrying conductive particles enter the target cells through the reversible electroporation to release the anti-tumor drug.

19. An electronic device, comprising:

a processor;

a memory electrically connected with the processor;

at least one program stored in the memory and configured to be executed by the processor, the at least one program configured to: a control method for achieving the inhibition of the diseased cell division system according to any of claims 13-17.

20. A computer-readable storage medium on which a computer program is stored, the computer program being characterized by implementing, when executed by an electronic device, the control method for suppressing a diseased cell division system according to any one of claims 13 to 17.