WO2024108481A1

WO2024108481A1 - Nanorobot and control method therefor

Info

Publication number: WO2024108481A1
Application number: PCT/CN2022/134040
Authority: WO
Inventors: 黄宏任; 王枫
Original assignee: 深圳先进技术研究院
Priority date: 2022-11-24
Filing date: 2022-11-24
Publication date: 2024-05-30

Abstract

A nanorobot, comprising: a shell (110), and a sodium-potassium pump (120), a field driving element (130) and a potential susceptor (140), which are provided in the shell (110), and an ultrasonic driving element (150), which is provided at a tail portion of the shell (110), wherein the sodium-potassium pump (120) is used for pumping extracellular high-concentration sodium ions into a matrix inside the shell (110), the field driving element (130) is used for driving the nanorobot to migrate toward an axon start segment, the potential susceptor (140) is used for recognizing identity information of a neuron, and the ultrasonic driving element (150) is used for driving, under ultrasonic waves of an external field, the nanorobot to move. The nanorobot carries a modified reverse-acting sodium-potassium pump (120), can continuously use a body's own ionic concentration change over a long period of time to achieve the regulation and control of neural activity, and can be widely applied to intervention in various neurological disorders related to excitatory/inhibitory imbalance of the nervous system; an axon hillock start segment of a specific neuron is identified by means of the potential susceptor (140) and the field driving element (130) which are carried on the nanorobot, such that a more precise targeted regulation and control effect can be achieved; and by means of the motion precise-control characteristic of ultrasonic waves of the ultrasonic driving element (150) combined with an imaging device, brain-region targeted motion of the nanorobot is implemented. Further provided is a control method for the nanorobot.

Description

A nanorobot and control method thereof

Technical Field

The present application relates to the field of medical device technology, and in particular to a nanorobot and a control method thereof.

Background technique

Studies have shown that there is an excitatory/inhibitory (E/I) imbalance in key neural circuits in neurological diseases such as epilepsy, Parkinson's disease, cognitive impairment, and depression. Imbalance in neuronal E/I can lead to abnormal discharge of its own electrical activity or even inactivation, affecting the execution of the body's normal functions. Therefore, maintaining the E/I balance of key neural nuclei is of great significance for the execution of normal functions of specific neurons and the maintenance of physiological homeostasis. The latest research has found that drugs such as neurotrophic factors can regulate E/I balance; nanorobot loading and delivery of drugs have also been successfully achieved in animal models; but there is still no clear clinical application for the long-term and targeted regulation of E/I balance in specific neurons.

Methods for human targeted regulation of brain neural activity include invasive electrical stimulation surgery, and non-invasive magnetic, electrical stimulation, ultrasound, and light regulation. Specific brain nuclei contain multiple types of neurons, which often play different roles. Therefore, it is necessary to target and precisely regulate specific neuron groups in specific brain regions to achieve emotional regulation and intervention in mental illness. In order to deliver drugs to targeted areas more efficiently and to exert regulatory functions more efficiently, nanorobots that can cross the blood-brain barrier and release drugs or other biomolecules are needed. In 1959, Feynman proposed that the miniaturization of machines to micro/nano sizes will bring new kinetic energy to the era. In recent years, many international teams have developed DNA nanorobots that can operate in the blood, detect cancer cells, and deliver proteins that cause blood coagulation; neutrophil hybrid nanorobots that have the ability to penetrate the blood-brain barrier and kill glioma cells in the brain; nanomachines with sound-light combined conversion and more precise regulation of neurons.

Existing nanorobots already have the characteristics of targeted neuronal regulation, but there are still some unresolved problems: ① Lack of identification of specific brain regions, especially specific neuronal groups in deep brain regions; ② Lack of effective regulation of E/I imbalance of neurons; ③ Drug delivery is time-sensitive and cannot exert long-term regulatory effects in the body; ④ How to combine nanorobots with medical equipment and apply them clinically to neural targeted regulation of the human brain; ⑤ Real-time imaging and guidance of nanorobots operating in the body are still difficult to achieve, etc.

Summary of the invention

In view of this, it is necessary to provide a nanorobot and a control method thereof that can perform precise targeted manipulation of specific neuronal groups in specific human brain regions in order to address the defects in the prior art.

To solve the above problems, this application adopts the following technical solutions:

One of the purposes of the present application is to provide a nanorobot, comprising a capsid, a sodium-potassium pump, a field driving element and a potential sensor arranged in the capsid, and an ultrasonic driving element arranged at the tail of the capsid, wherein the sodium-potassium pump is used to pump high-concentration extracellular sodium ions into the matrix in the capsid, the field driving element is used to drive the nanorobot to migrate toward the axon initiation segment, the potential sensor is used to identify the identity information of neurons, and the ultrasonic driving element is used to drive the nanorobot to move under ultrasonic waves in an external field.

In some embodiments, the capsid is a lipid-fused poly(acetic acid-glycolic acid-poly(ethylene glycol)) polymer.

In some embodiments, the sodium-potassium pump pumps sodium ions into the matrix along the concentration gradient in a reverse-acting manner.

In some of the embodiments, the field driving element utilizes the characteristics of abundant sodium ion channels expressed on the membrane surface of the axon initial segment and the potential energy difference formed with the surrounding when the action potential is emitted to drive the nanorobot to migrate toward the axon initial segment.

In some of the embodiments, anchoring microtubules are further included, wherein the anchoring microtubules are connected to the sodium-potassium pump, the field-driven element, and the potential sensor, and the anchoring microtubules are used to anchor the sodium-potassium pump, the field-driven element, and the potential sensor in the matrix.

In some embodiments, the head of the capsid has a cone-shaped structure.

The second object of the present application is to provide a control method of the nanorobot, comprising the following steps:

Planning the operation route of the nanorobot;

delivering the nanorobot into the blood vessel according to the running route;

The ultrasonic driving element guides the nanorobot to the target area;

The potential receptors determine the neuron type;

The field driving element drives the nanorobot to migrate toward the axon initiation segment;

The sodium-potassium pump transports high extracellular sodium ion concentrations into the matrix.

In some embodiments, the step of planning the running route of the nanorobot specifically includes the following steps:

The target area is scanned by a magnetic resonance imaging device to obtain the position coordinates of the target nucleus, and the route for the nanorobot to enter is planned according to the distribution of blood vessels.

In some embodiments, the step of delivering the nanorobot into the blood vessel according to the running route specifically includes the following steps:

The nanorobot is injected intravenously into a blood vessel according to the running route.

In some of the embodiments, in the step of guiding the nanorobot to the target area by the ultrasonic driving element, the nanorobot is driven to the target area by controlling the motion switch, speed and trajectory of the ultrasonic driving element.

This application adopts the above technical solution, and its beneficial effects are as follows:

The nanorobot and its control method provided by the present application are equipped with a modified reverse-acting sodium-potassium pump, which can utilize the body's own ion concentration changes for a long time and continuously to achieve regulation of neural activity, and can be widely used in the intervention of various neurological diseases related to the imbalance of excitation/inhibition of the nervous system; by using the onboard potential receptors and field driving elements to identify the axonal starting segment of specific neurons, a more precise targeted regulation effect can be achieved; by using the ultrasonic precise control movement characteristics of the ultrasonic driving element, combined with imaging equipment, the nanorobot's brain region targeted movement can be achieved. The nanorobot and its control method provided by the present application improve the existing nanorobots, and through the modified functional elements, targeted guidance, neuron identification and long-term regulation of the target brain region can be achieved.

BRIEF DESCRIPTION OF THE DRAWINGS

In order to more clearly illustrate the technical solutions of the embodiments of the present application, the drawings required for use in the embodiments of the present application or the description of the prior art will be briefly introduced below. Obviously, the drawings described below are only some embodiments of the present application. For ordinary technicians in this field, other drawings can be obtained based on these drawings without paying any creative work.

FIG1 is a schematic diagram of the structure of the nanorobot provided in Example 1 of the present application.

Figure 2 is a flow chart of the steps of the control method of the nanorobot provided in Example 2 of the present application.

Detailed ways

The embodiments of the present application are described in detail below, and examples of the embodiments are shown in the accompanying drawings, wherein the same or similar reference numerals throughout represent the same or similar elements or elements having the same or similar functions. The embodiments described below with reference to the accompanying drawings are exemplary and are intended to be used to explain the present application, and should not be construed as limiting the present application.

In the description of the present application, it should be understood that the terms "upper", "lower", "horizontal", "inside", "outside", etc., indicating orientations or positional relationships, are based on the orientations or positional relationships shown in the accompanying drawings, and are only for the convenience of describing the present application and simplifying the description, rather than indicating or implying that the device or element referred to must have a specific orientation, be constructed and operated in a specific orientation, and therefore should not be understood as a limitation on the present application.

In addition, the terms "first" and "second" are used for descriptive purposes only and should not be understood as indicating or implying relative importance or implicitly indicating the number of the indicated technical features. Therefore, a feature defined as "first" or "second" may explicitly or implicitly include one or more of the features. In the description of this application, the meaning of "plurality" is two or more, unless otherwise clearly and specifically defined.

In order to make the objectives, technical solutions and advantages of the present application more clearly understood, the present application is further described in detail below in conjunction with the accompanying drawings and embodiments.

The present application provides a nanorobot and a control method thereof, aiming to provide a brain-specific neuron manipulation system with the nanorobot as the core, so as to solve the problem that specific neuron groups in specific brain regions of humans are difficult to target and manipulate, and to provide a long-term and efficient regulation method for the treatment of human nervous system and psychiatric diseases.

Example 1

Please refer to FIG1 , which is a schematic diagram of the structure of a nanorobot provided in this embodiment 1, including a shell 110, a sodium-potassium pump 120 disposed in the shell 110, a field driving element 130 and a potential sensor 140, and an ultrasonic driving element 150 disposed at the tail of the shell 110. The specific implementation of each functional element is described in detail below.

In this embodiment, the capsid 110 is a lipid-fused polyacetic acid-hydroxyglycolic acid-polyethylene glycol polymer, which has certain mechanical properties and maintains the permeability of lipids, ensuring the entry and exit of ions into and out of the matrix, while being able to isolate the functional elements from the clearing effects of proteases and glial cells in brain tissues. The present application can construct a specific capsid shape by cross-linking microtubules.

Furthermore, the head of the capsid 110 is a conical structure 111, which helps the nanorobot to move in tissues.

The sodium-potassium pump 120 is disposed in the capsid 110 , and is used to pump extracellular high-concentration sodium ions into the matrix in the capsid 110 .

In this embodiment, the sodium-potassium pump 120 can utilize the characteristics of the gap between two action potential releases and the increase in extracellular sodium ion concentration to allow the sodium-potassium pump 120 to pump sodium ions into the nanorobot matrix along the concentration gradient in the opposite direction, thereby reducing the extracellular sodium ion concentration of the neuronal axon and reducing the frequency and duration of action potential release.

It can be understood that the sodium-potassium pump 120 can act in the opposite direction to synthesize ATPase under specific conditions, and in the interval between two action potentials, the sodium ions in the neuron cell will be transported to the extracellular space through the sodium-potassium pump, so that the extracellular sodium ion concentration increases, and then a large amount of sodium ions flow into the cell through the open sodium ion channels, so that the action potential is re-emitted. The sodium-potassium pump modified in this embodiment can utilize the characteristics of the interval between two potentials and the increase in extracellular sodium ion concentration to pump sodium ions into the nanorobot matrix and transport potassium ions at the same time, so that the re-emission of action potentials is delayed and the frequency of action potential emission is reduced, thereby achieving the purpose of regulating the excitation/inhibition balance of neurons.

The field driving element 130 is used to drive the nanorobot to migrate toward the axon starting segment.

In this embodiment, the field driving element 130 drives the nanorobot to migrate toward the axon starting segment by utilizing the characteristics of abundant sodium ion channels expressed on the membrane surface of the axon starting segment and the potential energy difference formed with the surrounding when the action potential is released.

It can be understood that due to the rich sodium ion channels on the membrane of the axon initial segment, its voltage threshold is low, and the movement to the axon initial segment is driven by charge-sensitive materials; when the initial action potential is released, the extracellular potential of the axon initial segment changes rapidly, which can drive the field potential difference-sensitive elements to target the axon hillock.

The potential sensor 140 is used to identify the identity information of neurons. Since different types of neurons have specific electrical fingerprint characteristics, the identity information of neurons can be identified through the potential sensor 140.

The ultrasonic driving element 150 is used to drive the nanorobot to move under the ultrasonic wave of the external field.

It can be understood that the ultrasonic driving element 150 can drive the nanorobot to move under the ultrasonic wave of the external field. By controlling the switch, speed and trajectory of the movement of the ultrasonic driving element 150, precise "on-demand movement" can be achieved, helping the nanorobot to penetrate tissue barriers through high-speed movement.

In this embodiment, the nanorobot further includes an anchoring microtube 160, which is connected to the sodium-potassium pump 120, the field-driven element 130 and the potential sensor 140, and is used to anchor the sodium-potassium pump 120, the field-driven element 130 and the potential sensor 140 in the matrix.

It can be understood that in this embodiment, a biocompatible matrix is used as a carrier, and the functional element can be anchored in the matrix of the nanorobot using the anchoring microtube 160.

The nanorobot provided in Example 1 of the present application is equipped with a modified reverse-acting sodium-potassium pump, which can continuously utilize the body's own ion concentration changes to achieve regulation of neural activity over a long period of time, and can be widely used in the intervention of various neurological diseases related to the imbalance of excitation/inhibition of the nervous system; by using the onboard potential receptors and field driving elements to identify the axonal starting segment of specific neurons, a more precise targeted regulation effect can be achieved; by using the ultrasonic driving element's ultrasonic precise control of movement characteristics, combined with imaging equipment, the nanorobot's brain region targeted movement is achieved. The above-mentioned nanorobot improves the existing nanorobots, and through the modified functional elements, it can achieve targeted guidance of the target brain region, neuron identification and long-term regulation. In actual applications, it can be divided into short-term and long-term regulation, and shallow and deep brain region regulation according to different intervention courses, so that the nanorobot can be equipped with different regulation and driving elements to perform precise individual intervention treatment.

Example 2

Please refer to FIG. 2 , which is a flowchart of a method for controlling a nanorobot provided in Embodiment 2, including steps S110 to S160 , and the implementation method of each step is described in detail below.

S110: Planning the running route of the nanorobot.

In this embodiment, the target area is scanned by a magnetic resonance imaging device to obtain the position coordinates of the target nucleus, and the route for the nanorobot to enter can be planned in combination with the distribution of blood vessels.

S120: Sending the nanorobot into the blood vessel according to the running route.

In some of the embodiments, the step of delivering the nanorobot into the blood vessel according to the operation route specifically includes the following steps: delivering the nanorobot into the blood vessel by intravenous injection according to the operation route.

It is understandable that in practice, the nanorobot is not limited to being delivered into the blood vessel by injection.

S130: The ultrasonic driving element 150 guides the nanorobot to the target area.

S140: The potential sensor 140 determines the neuron type.

It can be understood that in this process, the nanorobot's capsid is detached, and since different types of neurons have specific electrical fingerprint characteristics, the identity information of the neuron can be identified through the potential sensor 140.

S150: The field driving element 130 drives the nanorobot to migrate toward the axon starting segment.

It can be understood that due to the abundant sodium ion channels on the membrane of the axon initial segment, its voltage threshold is low, and the movement to the axon initial segment is driven by charge-sensitive materials; when the initial action potential is released, the extracellular potential of the axon initial segment changes rapidly, which can drive the field potential difference-sensitive elements to target the axon hillock.

S160: The sodium-potassium pump 120 transports the high-concentration extracellular sodium ions into the matrix.

The control method of the nanorobot provided in Example 2 of the present application is equipped with a modified reverse-acting sodium-potassium pump, which can use the body's own ion concentration changes for a long time and continuously to achieve the regulation of neural activity, and can be widely used in the intervention of various neurological diseases related to the imbalance of excitation/inhibition of the nervous system; the axonal starting segment of a specific neuron can be identified by the carried potential receptors and field drive elements, which can achieve more accurate targeted regulation; the characteristics of the ultrasonic drive element's ultrasonic precise control of movement, combined with imaging equipment, can achieve the targeted movement of the nanorobot in the brain area, the above-mentioned nanorobot improves the existing nanorobot, and realizes the targeted guidance, neuron identification and long-term regulation of the target brain area through the modified functional elements. In practical applications, it can be divided into short-term and long-term regulation according to different intervention courses; and shallow and deep brain area regulation, so that the nanorobot is equipped with different regulation and drive elements to carry out accurate individual intervention treatment. The successful implementation of this application is conducive to clinical transformation and provides new treatment methods for effective intervention of neuropsychiatric diseases such as epilepsy, depression, Parkinson's disease, etc.

It can be understood that the technical features of the above-described embodiments can be combined arbitrarily. In order to make the description concise, not all possible combinations of the technical features in the above-described embodiments are described. However, as long as there is no contradiction in the combination of these technical features, they should be considered to be within the scope of this specification.

The above are only preferred embodiments of the present application, and only specifically describe the technical principles of the present application. These descriptions are only for explaining the principles of the present application and cannot be interpreted as limiting the scope of protection of the present application in any way. Based on the explanation here, any modifications, equivalent substitutions and improvements made within the spirit and principles of the present application, and other specific implementation methods of the present application that can be associated with the technicians in this field without creative work, should be included in the scope of protection of the present application.

Claims

A nanorobot, characterized in that it includes a capsid, a sodium-potassium pump, a field driving element and a potential sensor arranged in the capsid, and an ultrasonic driving element arranged at the tail of the capsid, wherein the sodium-potassium pump is used to pump high-concentration extracellular sodium ions into the matrix in the capsid, the field driving element is used to drive the nanorobot to migrate toward the axon starting segment, the potential sensor is used to identify the identity information of neurons, and the ultrasonic driving element is used to drive the nanorobot to move under ultrasonic waves in an external field.
The nanorobot as described in claim 1 is characterized in that the capsid is a polyacetic acid-hydroxyglycolic acid-polyethylene glycol polymer fused with lipids.
The nanorobot as described in claim 1 is characterized in that the sodium-potassium pump pumps sodium ions into the matrix along the concentration gradient in a reverse direction.
The nanorobot as described in claim 1 is characterized in that the field driving element utilizes the characteristics of abundant sodium ion channels expressed on the membrane surface of the axon starting segment and the potential energy difference formed with the surrounding when the action potential is released to drive the nanorobot to migrate toward the axon starting segment.
The nanorobot as described in claim 1 is characterized in that it also includes an anchoring microtube, which is connected to the sodium-potassium pump, the field-driven element and the potential sensor, and the anchoring microtube is used to anchor the sodium-potassium pump, the field-driven element and the potential sensor in the matrix.
The nanorobot as described in claim 1 is characterized in that the head of the shell has a conical structure.
A method for controlling a nanorobot according to claim 1, characterized in that it comprises the following steps:

Planning the operation route of the nanorobot;

delivering the nanorobot into the blood vessel according to the running route;

The ultrasonic driving element guides the nanorobot to the target area;

The potential receptors determine the neuron type;

The field driving element drives the nanorobot to migrate toward the axon initiation segment;

The sodium-potassium pump transports high extracellular sodium ion concentrations into the matrix.
The control method of the nanorobot according to claim 7 is characterized in that, in the step of planning the running route of the nanorobot, the following steps are specifically included:

The target area is scanned by a magnetic resonance imaging device to obtain the position coordinates of the target nucleus, and the route for the nanorobot to enter is planned according to the distribution of blood vessels.
The control method of the nanorobot according to claim 7 is characterized in that, in the step of delivering the nanorobot into the blood vessel according to the running route, the following steps are specifically included:

The nanorobot is injected intravenously into a blood vessel according to the running route.
The nanorobot control method as described in claim 7 is characterized in that in the step of guiding the nanorobot to the target area by the ultrasonic driving element, the nanorobot is driven to the target area by controlling the motion switch, speed and trajectory of the ultrasonic driving element.