CN115068108A - Multi-wavelength photo-thermal and photodynamic melanoma laser therapeutic apparatus - Google Patents
Multi-wavelength photo-thermal and photodynamic melanoma laser therapeutic apparatus Download PDFInfo
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Abstract
The invention provides a multi-wavelength photo-thermal and photodynamic melanoma laser therapeutic apparatus, which comprises: a housing; at least one laser element and at least one fiber optic probe located within the housing; wherein the at least one laser element emits one or more laser light beams having a wavelength of 600nm-1350 nm. The laser therapeutic apparatus of the technical scheme of the invention utilizes melanin existing in melanoma as a photo-thermal and photodynamic photosensitizer, does not need to inject an external photosensitizer, solves the toxicity problem caused by photosensitizer injection, simultaneously induces photo-thermal and photodynamic therapy by the melanoma, has good targeting property, and solves the problem that the photosensitizer targets tumors.
Description
Technical Field
The invention relates to the technical field of biomedicine, in particular to a multi-wavelength photo-thermal and photodynamic melanoma laser therapeutic apparatus.
Background
The current major clinical treatments for melanoma include surgical resection, radiation therapy and chemotherapy, and light therapy, which has been emerging in recent years, is also widely used for the treatment of melanoma, and includes photothermal therapy and photodynamic therapy. Photothermal therapy is a therapeutic method in which a material having a high photothermal conversion efficiency is injected into the inside of a human body, is concentrated near tumor tissue by using a targeting recognition technology, and converts light energy into heat energy under the irradiation of an external light source (generally, near infrared light) to kill cancer cells. Photodynamic therapy is a new method for treating tumor diseases by using photosensitive drugs and laser activation, wherein a tumor part is irradiated by specific wavelength, so that the photosensitive drugs which are selectively gathered on tumor tissues can be activated to trigger photochemical reaction to destroy tumors. The photosensitive medicine in the new generation of photodynamic therapy can transfer energy to ambient oxygen to generate singlet oxygen with strong activity, and the singlet oxygen can generate oxidation reaction with nearby biomacromolecules to generate cytotoxicity so as to kill tumor cells.
For example, patent application No. 201810475100.8: a targeting peptide is adopted to modify nanoparticles and load a photosensitizer indocyanine green (ICG), and after the nanoparticles are subjected to transdermal administration, near infrared light is adopted to trigger the ICG to generate heat and release singlet oxygen.
Also for example, patent application No. 201910054759.0: a target phase-change nanoparticle carrying a PD1 antibody and a preparation method and application thereof are disclosed, the target phase-change nanoparticle carrying a PD1 antibody can be applied to preparation of an anti-melanoma drug, a PD1 antibody is delivered to a melanoma tissue in a targeted manner, the concentration of the PD1 antibody in the melanoma tissue is improved, meanwhile, T cell anti-tumor immune response in the melanoma tissue is enhanced by combining with photothermal treatment of Fe3O4 nanoparticles, and the treatment effect of the PD1 antibody is effectively improved.
However, the existing melanoma phototherapy means adopts a method of externally injecting a photosensitizer, but the photosensitizer often has the problems of poor biological toxicity and poor tumor targeting.
Disclosure of Invention
The invention mainly aims to provide a multi-wavelength photothermal and photodynamic melanoma laser therapeutic apparatus, and aims to solve the problem that the existing melanoma phototherapy means needs external injection of a photosensitizer.
In order to achieve the above object, the present invention provides a multi-wavelength photothermal and photodynamic melanoma laser therapeutic apparatus, comprising:
a housing;
at least one laser element and at least one fiber optic probe located within the housing;
wherein the at least one laser element emits one or more laser light beams having a wavelength of 600nm-1350 nm.
Optionally, the laser element includes a first laser element and a second laser element, the laser wavelength emitted by the first laser element is 750-1000nm, and the laser wavelength emitted by the second laser element is 1000-1350 nm.
Optionally, the laser therapeutic apparatus further comprises a third laser element, and the laser wavelength emitted by the third laser element is 600nm-750 nm.
Optionally, the power density of the laser is 0.1-2W/cm 2 The irradiation time is 5-20 min.
Optionally, the power density of the fiber optic probe is 0.5-1W/cm 2 The irradiation time is 5-10 min.
The invention also provides a melanoma treatment method, which comprises the following steps:
irradiating the melanoma part with one or more laser beams with the wavelength of 600nm-1350 nm;
invasive fiber optic irradiation of the melanoma site is performed using at least one fiber optic probe.
Optionally, the laser is two beams, and the two beams of laser are a first laser with a wavelength of 750-.
Optionally, the laser further comprises a third laser with a wavelength of 600nm-750 nm.
Optionally, the power density of the laser is 0.1-2W/cm 2 The irradiation time is 5-20 min.
Optionally, the power density of the fiber optic probe is 0.5-1W/cm 2 The irradiation time is 5-10 min.
The multi-wavelength photo-thermal and photodynamic melanoma laser therapeutic apparatus provided by the technical scheme of the invention utilizes melanin existing in melanoma as photo-thermal and photodynamic photosensitizer, does not need to inject external photosensitizer, solves the problem of toxicity caused by photosensitizer injection, simultaneously induces photo-thermal and photodynamic therapy by the melanoma, has good targeting property, solves the problem of photosensitizer targeting tumor, adopts multi-wavelength laser combination and invasive optical fiber irradiation, can solve the problem that the melanoma at the deep layer cannot be irradiated by intercepting most of light energy by surface melanin, can realize deep melanoma therapy, and kills the melanoma tissue at the deep layer.
Drawings
In order to more clearly illustrate the embodiments or technical solutions of the present invention, the drawings used in the embodiments or technical solutions of the prior art will be briefly described below, it is obvious that the drawings in the following description are only some embodiments of the present invention, and for those skilled in the art, other drawings can be obtained according to the structures shown in the drawings without creative efforts.
FIG. 1 is a graph showing the results of photothermal temperature comparison experiments for different tumor models according to an embodiment of the present invention;
FIG. 2 is a graph showing the results of photothermal temperature comparison experiments with different tumor models according to another embodiment of the present invention;
FIG. 3 is a graph showing the results of photothermal and photodynamic therapy of melanoma in accordance with the present invention.
The implementation, functional features and advantages of the objects of the present invention will be further explained with reference to the accompanying drawings.
Detailed Description
The technical solutions in the embodiments of the present invention will be clearly and completely described below with reference to the drawings in the embodiments of the present invention, and it is obvious that the described embodiments are only a part of the embodiments of the present invention, and not all of the embodiments. All other embodiments, which can be derived by a person skilled in the art from the embodiments given herein without making any creative effort, shall fall within the protection scope of the present invention.
The invention provides a multi-wavelength photo-thermal and photodynamic melanoma laser therapeutic apparatus which can directly perform phototherapy on melanoma without externally injecting a photosensitizer.
In an embodiment of the present invention, a multi-wavelength photothermal and photodynamic melanoma laser therapeutic apparatus is provided, which includes: a housing; at least one laser element and at least one fiber optic probe located within the housing; wherein the at least one laser element emits one or more laser light beams having a wavelength of 600nm-1350 nm.
Specifically, the shell forms the whole appearance structure of the laser therapeutic apparatus, and plays a role in protecting components inside the laser therapeutic apparatus. Wherein the laser element is selected from Er, YAG and pulsed CO 2 、Ho:YAG、Er:YAP、Er/Cr:YSGG、Ho:YSGG、Er:GGSG、Er:YLF、Tm:YAG、Ho/Nd:YAlO 3 Drilling: MgF 2 HF agents, DF agents, carbon monoxide, deep UV lasers, diode lasers, Nd: YAG lasers up to three times the frequency, and all combinations thereof.
Specifically, the fiber optic probe is used for being inserted into a melanoma part to carry out invasive laser irradiation and carry out phototherapy on a deeper part of the melanoma. The optical fiber probe has excellent performances of water resistance, high temperature resistance, chemical corrosion resistance, electromagnetic interference resistance, nuclear radiation resistance and the like. The wavelength of the light irradiated by the optical fiber probe can be the same as or different from that of the light emitted by the laser element, but the wavelength of the light irradiated by the optical fiber probe also can be 600nm-1350 nm.
The multi-wavelength photo-thermal and photodynamic melanoma laser therapeutic apparatus provided by the technical scheme of the invention utilizes melanin existing in melanoma as a photo-thermal and photodynamic photosensitizer, an external photosensitizer does not need to be injected, the problem of toxicity caused by photosensitizer injection is solved, meanwhile, the melanoma induces photo-thermal and photodynamic therapy, the targeting property is good, and the problem that the photosensitizer targets tumors is solved.
In an embodiment, the laser therapeutic apparatus can perform photothermal therapy, and the photothermal therapy adopts the combination of the laser of the near-infrared biological window i (750 + 1000nm) and the laser of the near-infrared biological window ii (1000 + 1350nm), compared with the near-infrared biological window i, the near-infrared biological window ii has a larger upper limit of the light exposure energy bearable of the skin and a better laser penetration depth, so as to realize deep melanoma therapy, and meanwhile, the laser therapeutic apparatus is combined with an invasive optical fiber probe to invade the interior of melanoma to kill the deep melanoma tissue.
Specifically, the laser element of the laser therapeutic apparatus may be one or two, the laser in the near-infrared biological window i and the laser in the near-infrared biological window ii may be sequentially emitted by the same laser element, the laser in the near-infrared biological window i may be first emitted, the laser in the near-infrared biological window ii may be first emitted, and the laser in the near-infrared biological window i and the laser in the near-infrared biological window ii may be sequentially emitted or simultaneously emitted by two different laser elements, which is not limited herein.
More specifically, the light irradiation of the fiber probe may be performed simultaneously with the laser or sequentially with the laser, and the irradiation sequence is not limited as well, and the light irradiation of the fiber probe may be performed before or after.
In another embodiment, the laser therapeutic apparatus can also perform photodynamic therapy, and the melanoma is irradiated by using visible light wavelength (600-.
Specifically, the light irradiation of the optical fiber probe may be performed simultaneously with the visible wavelength laser, or may be performed sequentially, and the light irradiation of the optical fiber probe may be performed before or after, which is not limited herein.
In a preferred embodiment, the laser therapeutic apparatus can perform photothermal therapy and photodynamic therapy, and combines the laser of the near-infrared biological window I (750-.
Specifically, the number of the laser elements of the laser therapeutic apparatus in this embodiment may be one, two, or three, which is not limited herein. When the laser element is one, the near-infrared biological window I laser, the near-infrared biological window II laser and the visible light wavelength laser are emitted by the same laser element in sequence, and the emission sequence is not limited. When two laser elements are provided, for example, the laser in the near-infrared biological window i and the laser in the near-infrared biological window ii can be emitted by the same laser element, and the laser in the visible wavelength can be emitted by the other laser element. When the number of the laser elements is three, the near-infrared biological window I laser, the near-infrared biological window II laser and the visible light wavelength laser are respectively emitted through different laser elements, the three lasers can be simultaneously irradiated or sequentially irradiated, and the sequence is not limited.
Optionally, the laser element includes a first laser element and a second laser element, the laser wavelength emitted by the first laser element is 750-1000nm, and the laser wavelength emitted by the second laser element is 1000-1350 nm.
Optionally, the laser therapeutic apparatus further comprises a third laser element, and the laser wavelength emitted by the third laser element is 600nm-750 nm.
Optionally, the power density of the laser is 0.1-2W/cm 2 The irradiation time is 5-20 min.
Optionally, the power density of the fiber optic probe is 0.5-1W/cm 2 The irradiation time is 5-10 min.
The invention also provides a melanoma treatment method, which comprises the following steps:
irradiating the melanoma part with one or more laser beams with the wavelength of 600nm-1350 nm;
invasive fiber optic irradiation of the melanoma site is performed using at least one fiber optic probe.
It can be understood that the laser irradiation of the melanoma site and the invasive fiber irradiation of the fiber probe to the melanoma site may be performed simultaneously or sequentially, and the laser irradiation may be performed before or after, which is not limited herein.
The melanoma treatment method provided by the technical scheme of the invention utilizes melanin existing in melanoma as a photo-thermal and photodynamic photosensitizer, does not need to inject an external photosensitizer, solves the toxicity problem caused by photosensitizer injection, simultaneously induces photo-thermal and photodynamic treatment by the melanoma, has good targeting property, and solves the problem that the photosensitizer targets tumors.
In one embodiment, the treatment method adopts the combination of the laser of the near-infrared biological window I (750-.
Specifically, the laser in the near-infrared biological window i and the laser in the near-infrared biological window ii may sequentially irradiate the melanoma site, or may simultaneously irradiate the melanoma site, which is not limited herein.
In another embodiment, the melanoma treatment method can also adopt visible light wavelength (600-.
In a preferred embodiment, the treatment method adopts a laser with a near-infrared biological window I (750-.
Specifically, the laser of the near-infrared biological window i, the laser of the near-infrared biological window ii and the laser of the visible light wavelength may irradiate the melanoma site simultaneously, or may irradiate sequentially, for example, the laser of the near-infrared biological window i and the laser of the near-infrared biological window ii may irradiate before the laser of the visible light wavelength, or may irradiate after the laser of the visible light wavelength, which is not limited herein.
Optionally, the laser is two beams, and the two beams of laser are a first laser with a wavelength of 750-.
Optionally, the laser further comprises a third laser with a wavelength of 600nm-750 nm.
Optionally, the power density of the laser is 0.1-2W/cm 2 The irradiation time is 5-20 min.
Optionally, the power density of the fiber optic probe is 0.5-1W/cm 2 The irradiation time is 5-10 min.
Embodiments of the present invention will be described in detail below with reference to specific examples, but those skilled in the art will appreciate that the following examples are only illustrative of the present invention and should not be construed as limiting the scope of the present invention. The examples, in which specific conditions are not specified, were conducted under conventional conditions or conditions recommended by the manufacturer. The reagents or instruments used are not indicated by the manufacturer, and are all conventional products available commercially.
Example 1 comparison of photothermal temperature increases for different tumor models
Three tumor models, namely B16 melanoma, A20 lymphoma and SMMC-7721 liver tumor, are selected, different tumors are illuminated, and the temperature rise of the three tumor models is observed after illumination is finished, so that the result is shown in figure 1. Wherein the temperature rise of the B16 melanoma model is obvious and is 0.5W/cm 2 The wavelength of the radiation is 808nm and 1064nm, the temperature can be raised to 62 ℃ after 10min of radiation, and the highest temperature can only be raised to 30 ℃ for A20 lymphoma and SMMC-7721 liver tumor which do not contain melanin, thereby fully indicating the photothermal conversion performance of the melanoma.
Example 2 comparison of photothermal temperature increases in different tumor models
Three tumor models of B16 melanoma, A20 lymphoma and HCT116 tumor were selected, and we compared the temperature rise of different tumors at 808nm and 1064nm laser wavelength, and the results are shown in FIG. 2 and Table 1. At 1W/cm 2 After 10min of laser irradiation, B16 melanoma rapidly increased to 130 degrees, whereas A20 and HCT116 tumors only increased 1-2 degrees. This further demonstrates the good photothermal conversion properties of melanoma itself.
TABLE 1 temperature rise of different tumors under near infrared irradiation
EXAMPLE 3 photothermal and photodynamic therapy for melanoma
In order to highlight the treatment effect of photothermal and photodynamic effects on melanoma, three tumor models of B16 melanoma, A20 lymphoma and SMMC-7721 liver tumor are selected as treatment contrast, wherein the A20 lymphoma and the SMMC-7721 liver tumor are tumor models without melanin.
The basic scheme is that 808nm and 1064nm combination of near-infrared laser with good penetrability and 630nm or 660nm visible-light-wavelength laser are adopted to irradiate the focus parts of three tumor models, namely B16 melanoma, A20 lymphoma and SMMC-7721 liver tumor, for larger tumors, the condition that the tumors cannot be eliminated by adopting non-contact laser is adopted, an optical fiber probe is adopted to invade the interior of the tumors, and the power density is 1W/cm 2 The irradiation time was 10min, and the treatment was performed every 1 day (0 day, 2 days, 4 days, …) to eliminate the tumor, and the results are shown in fig. 3. By comparing the treatment effects on different tumors, the B16 melanoma can achieve good treatment effect under the condition of illumination, the tumor volume is obviously reduced, and the ablation treatment effect on A20 and SMMC-7721 tumors cannot be achieved through illumination.
The above description is only an alternative embodiment of the present invention, and not intended to limit the scope of the present invention, and all modifications and equivalents of the present invention, which are made by the contents of the present specification and the accompanying drawings, or directly/indirectly applied to other related technical fields, are included in the scope of the present invention.
Claims (5)
1. The utility model provides a multi-wavelength light and heat, photodynamic melanoma laser therapeutic instrument which characterized in that includes:
a housing;
at least one laser element and at least one fiber optic probe located within the housing;
wherein the at least one laser element emits one or more laser light beams having a wavelength of 600nm to 1350 nm.
2. The multi-wavelength photothermal and photodynamic melanoma laser treatment instrument as claimed in claim 1, wherein the laser element comprises a first laser element and a second laser element, the laser wavelength emitted by the first laser element is 750- > 1000nm, and the laser wavelength emitted by the second laser element is 1000- > 1350 nm.
3. The multi-wavelength photothermal photodynamic melanoma laser treatment instrument as claimed in claim 2, wherein the laser treatment instrument further comprises a third laser element, and the laser wavelength emitted by the third laser element is 600nm to 750 nm.
4. The multi-wavelength photothermal photodynamic melanoma laser treatment instrument as claimed in claim 3, wherein the power density of the laser is 0.1-2W/cm 2 The irradiation time is 5-20 min.
5. The multi-wavelength photothermal and photodynamic melanoma laser treatment instrument as claimed in claim 4, wherein the power density of the optical fiber probe is 0.5-1W/cm 2 The irradiation time is 5-10 min.
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