Pulsed laser-responsive colloidal micro / nano robots, their fabrication methods and applications

Abstract

This invention belongs to the field of microrobot technology, specifically a pulsed laser-responsive colloidal micro / nanorobot, its preparation method, and its applications. The micro / nanorobot has a spherical structure, comprising a core layer and a functional layer from the inside out, with the functional layer covering the core layer. The core layer is a thermoresponsive phase change material, and the functional layer is a noble metal nanomaterial. The noble metal nanomaterial in the functional layer can absorb and convert near-infrared pulsed laser light into heat, causing a phase change in the core layer, driving the micro / nanorobot to achieve stepping motion and penetrate physical barriers. The micro / nanorobot is prepared through steps such as high-energy ultrasonic mechanical emulsification and chemical reduction. This micro / nanorobot can serve as a universal carrier for loading chemotherapy drugs, gene drugs, or photothermal therapeutic agents, achieving an integrated function of "barrier penetration-targeted drug delivery-synergistic therapy" for deep tumor delivery and blood-brain barrier penetration, providing a new technical pathway for the diagnosis and treatment of diseases such as glioma.

Description

Technical Field

[0001] This invention relates to the field of microrobot technology, specifically to a pulsed laser-responsive colloidal micro / nano robot, its preparation method, and its applications. Background Technology

[0002] One of the core bottlenecks in the clinical treatment of malignant tumors lies in the obstructive effect of physical barriers. For example, the blood-brain barrier is the primary obstacle to the treatment of gliomas. The blood-brain barrier is a specialized microvascular network composed of brain endothelial cells, which interconnect with pericytes, astrocytes, microglia, and neurons to form neurovascular units. Anatomically, the blood-brain barrier mainly refers to the cell interface formed by the tight junctions of brain capillary endothelial cells, which protects the central nervous system from the invasion of foreign macromolecules and harmful substances. This barrier can prevent more than 98% of small molecule drugs and almost all macromolecule drugs from effectively entering brain tissue to exert their therapeutic effects. Furthermore, the tumor lesion itself forms a physical matrix barrier composed of collagen fibers and extracellular matrix, which further hinders the penetration of nanocarriers into the deeper layers of the lesion. The combined effect of these two barriers ultimately makes it difficult for drug concentrations at the lesion site to reach effective therapeutic levels, significantly limiting clinical treatment outcomes.

[0003] In the field of traditional physical barrier penetration technology, solutions using mannitol or focused ultrasound exist, the core principle of which is to facilitate the passage of drug molecules or carriers by opening the barrier. However, the barrier opening effect achieved by such chemical or physical means is only temporary and cannot actively propel drugs or carriers to complete cross-barrier delivery. Therefore, its effect on improving the delivery efficiency of passive drug transport is very limited and cannot meet the clinical treatment requirements for efficient drug delivery. With the development of micro- and nano-technology, vascular micro- and nano-robots are gradually being applied to the field of drug delivery. These robots can circulate in the blood environment and accumulate in target tissues. Combined with drug loading capabilities, they can construct therapeutic systems based on active delivery. For example, in existing technologies, the neutrophil robot developed by Harbin Institute of Technology has achieved blood-brain barrier penetration through magnetic field navigation technology; the mitochondrial exocytosis-mediated drug delivery system developed by the West China Hospital team improves the penetration depth of drugs into tumor tissues through dynamic charge-flipping mechanisms and intracellular to intercellular delivery cycles.

[0004] Furthermore, Chinese patent document CN106474618A discloses a magnetically controlled micro soft crawling robot. This microrobot capsule includes a marking device comprising a fixing device, a piston, a spring, a nylon thread, a heater, a shielding device, and a tag device. This marking function enables medical personnel to activate the marking device and release the tag when the microrobot capsule reaches the target site, thereby achieving disease screening and marking at specific target sites, and also enabling drug release at the target site. In other words, this microrobot can crawl or turn under the drive of an alternating magnetic field, providing a basis for drug delivery. However, this prior art relies on an alternating magnetic field for driving, and the depth and uniformity of magnetic field penetration are affected by human tissues (such as bones and organs). Deep target sites may experience insufficient driving force and decreased turning accuracy.

[0005] Chinese patent document CN115025065A discloses a stimulus-responsive multifunctional targeted microrobot, its preparation method, and its application. This prior art provides a microrobot that can precisely control a magnetic field, guiding it to accurately target cancer cells and combining it with chemophotothermal therapy to achieve remarkable anti-tumor efficacy. However, this prior art robot relies on a magnetic field for precise targeting. The small size of the microrobot results in a limited content of internal magnetic elements, often requiring a strong external magnetic field to drive its stable movement in the complex in vivo environment. Furthermore, the magnetic field exhibits rapid decay, limiting the robot's working space. While the magnetic field generated by permanent magnets is strong enough, its uneven spatial distribution makes it difficult to consistently ensure precise drive when moving the robot towards deeper lesions, potentially leading to target deviation.

[0006] Chinese patent document CN117122553A discloses a microrobot for active targeted cell delivery and its preparation method. The microrobot comprises an azobenzene-modified magnetically controlled microrobot and PS@SiO2@Au-DNA nanoparticles. The azobenzene-modified magnetically controlled microrobot includes an inner layer of microrobots with a magnetic coating on its surface. A SiO2 layer is formed on the surface of the magnetic coating, and the azobenzene modification is applied to the outer side of the SiO2 layer. The PS@SiO2@Au-DNA nanoparticles include cyclodextrin-modified PS@SiO2 microspheres in the inner layer. An Au layer is formed on one side of each cyclodextrin-modified PS@SiO2 microsphere, and a DNA aptamer-modified layer is formed on the surface of the Au layer. This prior art utilizes supramolecular assembly through the modification of the intermediate microspheres to enable the microrobot to form a controllable connection and release with cells. Its cell-targeting delivery capability is evaluated using an adjustable magnetic field, achieving cell capture, targeted transport, and controllable release of the microrobot, improving cell loading efficiency, and realizing controllable cell release and robot retrieval. The existing technology relies on a magnetic coating on the surface to achieve magnetic navigation. However, this design always faces the dilemma of magnetic control capability and cell safety, making it difficult to achieve accurate navigation and potentially leading to problems such as target deviation and motion stagnation.

[0007] However, existing vascular micro- and nanorobot technologies still have significant limitations. On the one hand, although the mobility of micro- and nanorobots can improve drug delivery distance, most existing vascular micro- and nanorobots adopt static structural designs of solid nanospheres or mesoporous spheres. Such structures are difficult to dynamically adjust their configuration according to the size differences between the blood-brain barrier and the tumor matrix barrier, resulting in the robot's inability to adapt well to the scale requirements of different physical barriers, further limiting the cross-barrier delivery effect.

[0008] In summary, existing micro / nanorobot drug delivery technologies are significantly limited in their ability to adjust size and dynamically transform configurations due to the influence of fixed static structures. Therefore, developing nanorobots with flexible, dynamically variable configurations and the ability to collaboratively penetrate multiple levels of biophysical barriers has become a key technological direction for solving the diagnostic and treatment challenges of central nervous system diseases such as gliomas, and is of great significance for promoting the development of treatment technologies for central nervous system diseases. Summary of the Invention

[0009] The purpose of this invention is to provide a pulsed laser-responsive colloidal micro / nanorobot, its preparation method, and its application. This pulsed laser-responsive colloidal micro / nanorobot has flexible dynamic configuration and can synergistically penetrate multiple levels of biophysical barriers. It can solve the core problem of low drug delivery efficiency in the diagnosis and treatment of malignant tumors such as glioma and stroke due to the fixed static structure and lack of barrier opening function of existing micro / nanorobots, which makes it difficult to effectively deliver drugs to deep tumors and penetrate the blood-brain barrier and tumor matrix barrier.

[0010] To solve the aforementioned technical problems, the present invention specifically adopts the following technical solution:

[0011] A first aspect of the present invention is to provide a pulsed laser-responsive colloidal micro / nano robot, the micro / nano robot having a spherical structure comprising a core layer and a functional layer from the inside out, the functional layer covering the core layer; the core layer being a pulsed laser-responsive material, the functional layer being a noble metal nanomaterial, the pulsed laser-responsive material absorbing and converting near-infrared pulsed laser light into thermal energy, causing a phase transition in the core layer, thereby driving the micro / nano robot to achieve stepping motion and penetrate physical barriers.

[0012] Preferably, the core layer comprises liquid perfluorocarbon, and the functional layer comprises palladium nanoparticles, gold nanoparticles, or silver nanoparticles; the functional layer absorbs near-infrared pulsed laser light and converts the light energy into heat energy, thereby triggering the cavitation phase transition of the liquid perfluorocarbon in the core layer, causing dynamic configuration transformation, achieving stepping motion, and penetrating physical barriers.

[0013] Preferably, the micro-nano robot further includes a modification layer located on the outer surface of the functional layer, the modification layer comprising one or more of polydopamine, poly-L-dopa, polytannic acid, and gelatin.

[0014] Preferably, the liquid perfluorocarbon is perfluoropentane or / and perfluorohexane, prepared by high-energy ultrasonic mechanical emulsification to form uniform droplets with a particle size of 0.05-50 μm; thereby making the initial particle size of the micro-nano robot 0.05-50 μm; the selection of the liquid perfluorocarbon is adjusted according to the phase transition temperature requirement.

[0015] Preferably, the functional layer is palladium nanoparticles, which are prepared by reducing tetrachloropalladium acid with ascorbic acid and have a particle size of 5-60 nm. The palladium nanoparticles possess the ability to absorb and convert near-infrared pulsed laser light, converting light energy into heat energy to precisely trigger the phase transition process of the liquid perfluorocarbon in the core layer.

[0016] Preferably, when the modifying layer is polydopamine, the polydopamine is formed by dispersing dopamine hydrochloride in an alkaline solution with a pH of 8.5, followed by oxidative polymerization upon exposure to air; the alkaline solution is one of tris(hydroxymethyl)aminomethane (Tris) buffer solution, sodium hydroxide (NaOH) solution, and phosphate buffered saline (PBS). Polydopamine can significantly improve the hydrophilicity and stability of colloidal nanorobots.

[0017] Preferably, the alkaline solution is a Tris buffer solution.

[0018] Preferably, the initial particle size of the micro-nano robot is 0.05-50 μm; the setting of the initial particle size of the micro-nano robot enables the core layer of liquid perfluorocarbon to rapidly vaporize after being triggered by a near-infrared pulsed laser, thus propelling the robot to achieve stepping motion.

[0019] Preferably, the selection of the liquid perfluorocarbon can be adjusted according to the phase transition temperature requirement. Perfluoropentane has a phase transition temperature of approximately 29°C, suitable for triggering scenarios near body temperature; perfluorohexane has a phase transition temperature of approximately 56°C, requiring precise control of the triggering timing in conjunction with near-infrared photothermal effects.

[0020] Using the above technical solution, the phase transition-motion synergistic mechanism is as follows: Under near-infrared pulsed laser irradiation, the functional layer Pd NPs absorb light energy and convert it into heat energy, causing the core layer liquid perfluorocarbon to rapidly vaporize and generate microbubbles; when the microbubbles expand, they generate outward mechanical force, which propels the nanorobots to achieve stepping motion; when the microbubbles contract, they form local negative pressure, which pulls the robot to move towards the lesion area. At the same time, the mechanical force of the microbubbles can temporarily open the tight connection of the blood-brain barrier and the fibrous structure of the tumor matrix barrier, providing a channel for the robot to penetrate.

[0021] A first aspect of the present invention is to provide a method for preparing the pulsed laser-responsive colloidal micro / nanorobot described in the first aspect of the present invention, comprising the following steps:

[0022] Preparation of the S1 micro / nano robot core layer: 20-500 μL of perfluorohexane was dispersed in 1-5 mL of a nonionic copolymer solution with a mass concentration of 0.1-0.5%, emulsified by ultrasound, and collected by centrifugation to obtain perfluorocarbon droplets;

[0023] Assembly of the S2 micro / nanorobot functional layer: Disperse perfluorocarbon droplets in 2-15 mL of deionized water to a volume concentration of 2-10%, add 0.5-1.5 mL of 10 mM tetrachloropalladic acid, and stir for 2-12 h; then quickly add 0.2-1 mL of 0.1 mg / mL ascorbic acid solution, react for 2-4 h, collect by centrifugation, and obtain perfluorocarbon droplets with assembled palladium nanoparticles, thus obtaining the micro / nanorobot.

[0024] Preferably, the process further includes step S3, assembly of the micro / nano robot modification layer: the assembled palladium nanoparticles are dispersed in 5-25 mL of a 10 mM Tris solution with a pH of 8.5, and 0.5-5 mL of a 0.5 mg / mL dopamine hydrochloride solution is added. The mixture is then exposed to air at 25°C and stirred for 24 h. After centrifugation, the assembled and modified micro / nano robots are obtained.

[0025] Preferably, the nonionic copolymer solution is a Pronic F-127 solution.

[0026] Specifically, the method for preparing the pulsed laser-responsive colloidal micro / nano robot includes the following steps:

[0027] S01: Disperse 20-500 μL of perfluorohexane (or perfluoropentane) in 1-5 mL of 0.1-0.5% Pronic F-127 solution, and sonicate at 20 kHz and 50-90 W for 1-5 min at 20-35℃. After emulsification, centrifuge at 8000-12000 rpm for 5-10 min and collect the precipitate at the bottom as perfluorocarbon droplets.

[0028] S02: Disperse the perfluorocarbon droplets obtained in step S01 in 2-15 mL of deionized water, controlling the droplet volume concentration to 2-10%; add 0.5-1.5 mL of 10 mM tetrachloropalladic acid solution, stir at room temperature for 2-12 h, so that tetrachloropalladic acid is uniformly adsorbed on the droplet surface; then quickly add 0.2-1 mL of 0.1 mg / mL ascorbic acid solution, react at room temperature for 2-4 h, the ascorbic acid reduces tetrachloropalladic acid to PdNPs and assembles them in situ on the droplet surface; finally, centrifuge at 8000-12000 rpm for 5-10 min, collect the perfluorocarbon droplets assembled with Pd NPs, and complete the functional layer assembly.

[0029] S03: Disperse the perfluorocarbon droplets of Pd NPs assembled in step 2 into 5-25 mL of 10 mM Tris solution (pH=8.5), and slowly add 0.5-5 mL of 0.5 mg / mL dopamine hydrochloride solution; stir for 24 h at 25 °C under air exposure, and dopamine hydrochloride will oxidize and polymerize on the droplet surface to form a polydopamine modified layer; finally, centrifuge at 8000-12000 rpm for 5-10 min, and collect the precipitate to obtain the complete responsive colloidal nanorobot.

[0030] Preferably, in step S1, the reaction temperature is 20-35℃, the ultrasonic frequency is 20kHz, the power is 30-90W, and the ultrasonic time is 0.5-5min; the centrifugation speed in steps S1, S2, and S3 is 1000-12000rpm, and the centrifugation time is 1-10min. The ultrasonic time in step S1 can be adjusted according to the droplet size requirements; 0.5min of ultrasonication can obtain droplets with a diameter of approximately 50μm; 1min of ultrasonication can obtain droplets with a diameter of approximately 10μm; and 5min of ultrasonication can obtain droplets with a diameter of less than 0.1μm.

[0031] Furthermore, the concentration of Pronic F-127 as an emulsifying stabilizer needs to be controlled between 0.1% and 0.5%. Too low a concentration can easily lead to droplet aggregation, while too high a concentration can increase the difficulty of subsequent cleaning. The optimal condition for the Tris solution to oxidatively polymerize dopamine hydrochloride is pH=8.5. When the pH is below 7.0, the polymerization reaction is slow, and when the pH is above 9.0, irregular polydopamine precipitates are easily formed.

[0032] A third aspect of the present invention is to provide an application of pulsed laser-responsive colloidal micro / nanorobots in the preparation of drug delivery systems.

[0033] Preferably, the drug delivery system includes a drug-loaded molecule for targeted delivery, or a carrier for in vitro photodynamic therapy drugs loaded into cells, or a carrier for photocatalysts in photocatalytic therapy.

[0034] Preferably, the application includes preparing the micro-nanorobot into a relevant targeting carrier for the treatment of central nervous system diseases.

[0035] Preferably, the application includes preparing the microrobot as a relevant targeting carrier for the treatment of malignant brain tumors.

[0036] Preferably, the malignant brain tumor includes a glioma.

[0037] Preferably, the central nervous system disease includes stroke.

[0038] Beneficial technical effects:

[0039] (1) First, the micro-nano robot has flexible dynamic configuration change characteristics. The liquid perfluorocarbon in its core layer undergoes a phase transition after absorbing near-infrared pulsed laser, driving the robot to achieve stepping motion and penetrate physical barriers. This dynamic configuration conversion capability enables the robot to flexibly adjust its shape according to the size difference between the blood-brain barrier and the tumor matrix barrier, thereby well adapting to the scale requirements of different physical barriers and significantly improving the cross-barrier delivery effect.

[0040] (2) The micro-nano robot uses noble metal nanomaterials as the functional layer, which can convert light energy into heat energy and precisely trigger the phase change process of liquid perfluorocarbon in the core layer. The functional layer absorbs near-infrared pulsed laser and converts light energy into heat energy, triggering the cavitation phase change of liquid perfluorocarbon in the core layer, forming a synergistic effect, that is, the rapid vaporization of the core layer propels the robot to achieve stepping motion, enabling the micro-nano robot to penetrate physical barriers.

[0041] (3) The micro-nanorobot uses polydopamine as a modification layer, which can significantly improve the hydrophilicity and stability of the colloidal nanorobot. The surface of the polydopamine modification layer is rich in functional groups such as hydroxyl and amino groups, which enhances the hydrophilicity of the colloidal layer; at the same time, it can reduce serum protein adsorption and prolong the cycle time of the nanorobot.

[0042] (4) The preparation method of the present invention is simple, and the micro-nano robot is prepared by high-energy ultrasonic mechanical emulsification and chemical reduction. Moreover, the method has high repeatability and controllability, which is conducive to realizing large-scale production and application.

[0043] (5) The present invention can prepare colloidal nanorobots with different particle sizes by adjusting the type of liquid perfluorocarbon in the core layer, the particle size of Pd NPs, or the thickness of polydopamine modification; and the application flexibility of the micro-nanorobots is strong. They can be used as universal carriers to load chemotherapy drugs, gene drugs or photothermal therapy agents, and can penetrate the blood-brain barrier to deliver drugs directly to the lesion site, realizing the integrated function of "barrier penetration-targeted drug delivery-synergistic treatment", providing a new technical path for the diagnosis and treatment of glioma, stroke and other central nervous system diseases. Attached Figure Description

[0044] To more clearly illustrate the technical solutions in the embodiments of the present invention or the prior art, the drawings used in the description of the embodiments or the prior art will be briefly introduced below. In all the drawings, similar elements or parts are generally identified by similar reference numerals. The elements or parts in the drawings are not necessarily drawn to scale. Obviously, the drawings described below are some embodiments of the present invention, and those skilled in the art can obtain other drawings based on these drawings without creative effort.

[0045] Figure 1 A transmission electron microscope image of a responsive colloidal nanorobot prepared according to a specific embodiment 1 of the present invention;

[0046] Figure 2 The particle size distribution of the responsive colloidal nanorobot prepared in Specific Embodiment 1 of the present invention;

[0047] Figure 3 The full X-ray photoelectron spectrum of the responsive colloidal micro / nanorobot prepared in Specific Embodiment 1 of the present invention;

[0048] Figure 4 Fine X-ray photoelectron spectroscopy of Pd element in responsive colloidal micro / nano robots prepared according to specific embodiment 1 of the present invention;

[0049] Figure 5 An optical microscope image of the micrometer-scale responsive colloidal micro / nanorobots prepared in specific embodiment 2 of the present invention;

[0050] Figure 6 An optical microscope image of the responsive colloidal microrobot prepared in specific embodiment 3 of the present invention;

[0051] Figure 7 The motion trajectory of the responsive colloidal nanorobot prepared in Specific Embodiment 2 of the present invention, without the application of pulsed laser drive, is shown in Specific Embodiment 4.

[0052] Figure 8 The motion trajectory of the responsive colloidal nanorobot prepared in Specific Embodiment 2 of the present invention under 2W pulsed laser drive using the method in Specific Embodiment 4;

[0053] Figure 9 The motion trajectory of the responsive colloidal nanorobot prepared in Specific Embodiment 2 of the present invention under 3W pulsed laser drive using the method in Specific Embodiment 4;

[0054] Figure 10 The motion trajectory of the responsive colloidal nanorobot prepared in Specific Embodiment 3 of the present invention under the driving of a 2W pulsed laser in Specific Embodiment 4;

[0055] Figure 11 The mean square displacements of the 10 μm responsive colloidal nanorobot prepared in Example 2 and the 50 μm responsive colloidal nanorobot prepared in Example 3, under different power pulsed laser drives, are measured using the method described in Example 4; where red represents... Figure 7 10μm micro-nano robots without pulsed laser illumination; green represents Figure 8 A 2W pulsed laser is applied to a 10μm micro / nano robot; purple represents... Figure 9 A 10μm micro / nano robot is subjected to a 3W pulsed laser; blue represents... Figure 10 A 2W pulsed laser is applied to a 50μm micro / nano robot;

[0056] Figure 12 According to the present invention Figure 11 The diffusion coefficients of motion for each group were calculated from the MSD data; Group 1 consisted of a 10μm micro / nano robot without pulsed laser irradiation; Group 2 consisted of a 10μm micro / nano robot with a 2W pulsed laser; Group 3 consisted of a 10μm micro / nano robot with a 3W pulsed laser; and Group 4 consisted of a 50μm micro / nano robot with a 2W pulsed laser.

[0057] Figure 13 According to the present invention Figure 12The average motion velocity of each group was calculated from the diffusion coefficient data; among them, group 1 is a 10μm micro / nano robot without pulsed laser irradiation; group 2 is a 10μm micro / nano robot with 2W pulsed laser irradiation; group 3 is a 10μm micro / nano robot with 3W pulsed laser irradiation; and group 4 is a 50μm micro / nano robot with 2W pulsed laser irradiation.

[0058] Figure 14 The motion image is obtained by the macroscopic recording method of Example 5 when the responsive colloidal nanorobot prepared in Example 2 is driven by a pulsed laser.

[0059] Figure 15 The in vivo distribution of responsive colloidal nanorobots with a size of less than 0.1 μm prepared by the method of Specific Example 1 of the present invention, after being labeled with indocyanine green and injected into a GL261 mouse subcutaneous tumor animal model, before and after the application of pulsed laser; (a) is the in vivo distribution before the application of pulsed laser, and (b) is the in vivo distribution after the application of pulsed laser.

[0060] Figure 16 This is a schematic diagram illustrating the principle and structure of the pulsed laser-responsive colloidal micro / nano robot of the present invention. Detailed Implementation

[0061] To make the objectives, technical solutions, and advantages of the embodiments of the present invention clearer, the technical solutions of the embodiments of the present invention will be clearly and completely described below with reference to the accompanying drawings. Obviously, the described embodiments are only some, not all, of the embodiments of the present invention. All other embodiments obtained by those skilled in the art based on the embodiments of the present invention without creative effort are within the scope of protection of the present invention.

[0062] In this document, "and / or" includes any and all combinations of one or more of the listed related items.

[0063] In this article, "multiple" means two or more, that is, it includes two, three, four, five, etc.

[0064] As used in this specification, the term "about" typically means + / -5% of the value, more typically + / -4%, more typically + / -3%, more typically + / -2%, even more typically + / -1%, and even more typically + / -0.5%.

[0065] Definition: In colloidal micro-nano robots, "colloidal body" is a simplified expression of colloidal-based functional body, specifically referring to a micro-nano scale aggregate with colloidal particles as the core building unit and possessing autonomous movement or specific functions.

[0066] Example: Figure 16 As shown, this pulsed laser-responsive colloidal micro / nanorobot has a spherical structure comprising a core layer and a functional layer from the inside out, with the functional layer covering the core layer. The core layer is a pulsed laser-responsive material, and the functional layer is a noble metal nanomaterial. The pulsed laser-responsive material can absorb and convert near-infrared pulsed laser light into thermal energy, causing a phase transition in the core layer and driving the micro / nanorobot to achieve stepping motion and penetrate physical barriers. The core layer includes liquid perfluorocarbon, and the functional layer includes palladium nanoparticles, gold nanoparticles, or silver nanoparticles. The functional layer absorbs near-infrared pulsed laser light and converts the light energy into thermal energy, thereby triggering a cavitation phase transition in the liquid perfluorocarbon in the core layer, resulting in a dynamic configurational transformation, enabling stepping motion and penetration of physical barriers. The micro / nanorobot also includes a modification layer located on the outer surface of the functional layer, which comprises one or more of polydopamine, poly-L-DOPA, polytannic acid, and gelatin. The liquid perfluorocarbon is perfluoropentane and / or perfluorohexane, prepared by high-energy ultrasonic mechanical emulsification to form uniform droplets with a particle size of 0.05-50 μm; the functional layer includes palladium nanoparticles, which are prepared by reducing tetrachloropalladium acid with ascorbic acid, and have a particle size of 5-60 nm. The palladium nanoparticles have the ability to absorb and convert near-infrared pulsed laser light, converting light energy into heat energy, and precisely triggering the phase transition process of the core layer liquid perfluorocarbon; the polydopamine is formed by dispersing dopamine hydrochloride in an alkaline solution with a pH of 8.5 and then exposing it to air for oxidative polymerization; the alkaline solution includes one of tris(hydroxymethyl)aminomethane (Tris) buffer solution, sodium hydroxide (NaOH) solution, and phosphate buffered solution (PBS).

[0067] In some specific embodiments, the alkaline solution is a Tris buffer solution.

[0068] The initial particle size of this micro-nano robot is 0.05-50 μm. This initial particle size setting allows for rapid vaporization of the core layer's liquid perfluorocarbon after near-infrared pulsed laser triggering, propelling the robot into stepping motion. The selection of the liquid perfluorocarbon can be adjusted according to the phase transition temperature requirements. Perfluoropentane has a phase transition temperature of approximately 29°C, suitable for triggering scenarios near body temperature; perfluorohexane has a phase transition temperature of approximately 56°C, requiring precise control of the triggering timing in conjunction with near-infrared photothermal effects.

[0069] The method for fabricating the pulsed laser-responsive colloidal micro / nano robots includes the following steps:

[0070] Preparation of the S1 micro / nano robot core layer: 20-500 μL of perfluorohexane was dispersed in 1-5 mL of a nonionic copolymer solution with a mass concentration of 0.1-0.5%, emulsified by ultrasound, and collected by centrifugation to obtain perfluorocarbon droplets; in some specific embodiments, the nonionic copolymer solution was Pronic F-127 solution;

[0071] Assembly of the S2 micro / nano robot functional layer: Disperse perfluorocarbon droplets in 2-15 mL of deionized water to a volume concentration of 2-10%, add 0.5-1.5 mL of 10 mM tetrachloropalladic acid, and stir for 2-12 h; then quickly (within 1 min) add 0.2-1 mL of 0.1 mg / mL ascorbic acid solution, react for 2-4 h, collect by centrifugation, and obtain perfluorocarbon droplets with assembled palladium nanoparticles, thus obtaining the micro / nano robot;

[0072] Assembly of the S3 micro / nano robot modification layer: Disperse the assembled palladium nanoparticles in perfluorocarbon droplets in 5-25 mL of a 10 mM Tris solution with a pH of 8.5, add 0.5-5 mL of a 0.5 mg / mL dopamine hydrochloride solution, and stir in air at 25°C for 24 h. Collect by centrifugation to obtain the assembled and modified micro / nano robots. In step S1, the reaction temperature is 20-35°C, the ultrasonic frequency is 20 kHz, the power is 30-90 W, and the ultrasonic time is 0.5-5 min. In steps S1, S2, and S3, the centrifugation speed is 1000-12000 rpm, and the centrifugation time is 1-10 min.

[0073] Application of pulsed laser-responsive colloidal micro / nanorobots in the preparation of drug delivery systems.

[0074] The drug delivery system includes loading drug molecules for targeted delivery, loading them into cells as a carrier for in vitro photodynamic therapy drugs, or loading photocatalysts in photocatalytic therapy.

[0075] Specifically, the application includes fabricating the micro-nanorobot into a relevant targeting carrier for the treatment of central nervous system diseases.

[0076] Specifically, the application includes fabricating the microrobot into a relevant targeting vector for tumor treatment.

[0077] Specifically, the tumor includes glioma.

[0078] Specifically, the central nervous system diseases include stroke.

[0079] Specific Example 1: This example provides a method for preparing nanoscale responsive colloidal nanorobots with a diameter of less than 0.1 μm. The specific steps are as follows:

[0080] Step 1: Prepare a 0.1% (w / w) aqueous solution of Pronic F-127 for later use;

[0081] Step 2: Measure 100 μL of perfluorohexane and add it to 3 mL of the Pronic F-127 aqueous solution prepared in Step 1. Emulsify the solution by ultrasonication at 20 kHz and 90 W for 3 min at 25°C to form a perfluorohexane droplet suspension.

[0082] Step 3: Centrifuge the suspension obtained in Step 2 at 10,000 rpm for 8 min, discard the supernatant and collect the bottom precipitate; wash the precipitate twice with deionized water, centrifuging at 10,000 rpm for 5 min after each wash to obtain purified perfluorohexane droplets.

[0083] Step 4: Disperse the perfluorocarbon droplets obtained in Step 3 in 6 mL of deionized water and stir magnetically (500 rpm) to ensure uniform dispersion of the droplets; add 0.5 mL of 10 mM tetrachloropalladium acid solution and stir at room temperature for 2 h; then add 0.5 mL of 0.1 mg / mL ascorbic acid solution and continue stirring at room temperature for 2 h.

[0084] Step 5: Centrifuge the mixture obtained in Step 4 at 10,000 rpm for 8 min, discard the supernatant, and wash the precipitate twice with deionized water to obtain perfluorocarbon droplets for assembling Pd NPs.

[0085] Step 6: Prepare a 10 mM Tris solution (pH=8.5), disperse the precipitate obtained in Step 5 in 5 mL of this Tris solution, and stir magnetically (at a speed of 300 rpm) to ensure uniform dispersion of the precipitate; slowly add 2 mL of a 0.5 mg / mL dopamine hydrochloride solution, and expose to air at 25 °C for 24 h with stirring.

[0086] Step 7: Centrifuge the mixture obtained in Step 6 at 10000 rpm for 8 min, discard the supernatant, wash the precipitate 3 times with deionized water, and finally disperse the precipitate in 2 mL of deionized water to obtain a responsive colloidal nanorobot suspension with a concentration of 0.5 mg / mL, and store at 4℃.

[0087] Figure 1 This is a transmission electron microscope image of a nanoscale responsive colloidal robot prepared according to a specific embodiment 1 of the present invention. The nanorobot prepared by the present invention has a spherical structure, uniform size, and a diameter of less than 0.1 μm. The core layer is a dark perfluorocarbon droplet, the surface is uniformly coated with a light-colored Pd NPs layer, and the outermost layer is a polydopamine modification layer (about 5 nm thick).

[0088] Figure 2 The figure shows the dynamic light scattering particle size distribution curve of the responsive colloidal nanorobot prepared in a specific embodiment of the present invention. As can be seen from the figure, the nanorobot prepared by the present invention has a narrow particle size distribution range (PDI=0.2) and an average particle size of 0.053 μm, and has good dispersibility in aqueous solution.

[0089] Figure 3 This is the X-ray photoelectron spectrum of the responsive colloidal micro / nanorobot prepared according to specific embodiment 1 of the present invention; Figure 4 This is a fine X-ray photoelectron spectrum of Pd elemental energy for colloidal micro / nanorobots. From Figure 3 It can be seen that the prepared nanorobots contain five elements: C, F, O, N, and Pd. The F element comes from the core layer perfluorocarbon, the Pd element comes from the functional layer, and the C, N, and O elements mainly come from the polydopamine modification layer. Figure 4 It can be seen that the binding energies at 335.2 eV and 340.5 eV correspond to Pd. 0 3D 5 / 2 and 3D 3 / 2 This indicates the presence of elemental Pd NPs in the nanorobots. Furthermore, the values ​​at 337.5 eV and 342.8 eV correspond to Pd... 2+ 3D 5 / 2 and 3D 3 / 2 This is because Pd coordinates with polydopamine, with Pd... 2+ It exists in the form of.

[0090] Specific Example 2: This example provides a method for preparing a pulsed laser-responsive colloidal robot with a diameter less than 10 μm. The specific steps are as follows:

[0091] Step 1: Prepare a 0.1% (w / w) aqueous solution of Pronic F-127 for later use;

[0092] Step 2: Measure 100 μL of perfluorohexane and add it to 3 mL of the Pronic F-127 aqueous solution prepared in Step 1. Emulsify the solution at 25°C with an ultrasonic frequency of 20 kHz and a power of 90 W for 1 min to form a perfluorohexane droplet suspension.

[0093] Step 3: Centrifuge the suspension obtained in Step 2 at 8000 rpm for 3 min, discard the supernatant and collect the bottom precipitate; wash the precipitate twice with deionized water, centrifuging at 8000 rpm for 3 min after each wash to obtain purified perfluorohexane droplets;

[0094] Step 4: Disperse the perfluorocarbon droplets obtained in Step 3 in 6 mL of deionized water and stir magnetically (500 rpm) to ensure uniform dispersion of the droplets; add 0.5 mL of 10 mM tetrachloropalladium acid solution and stir at room temperature for 2 h; then add 0.5 mL of 0.1 mg / mL ascorbic acid solution and continue stirring at room temperature for 2 h.

[0095] Step 5: Centrifuge the mixture obtained in Step 4 at 8000 rpm for 3 min, discard the supernatant, wash the precipitate twice with deionized water to obtain perfluorocarbon droplets for assembling Pd NPs;

[0096] Step 6: Prepare a 10 mM Tris solution (pH=8.5), disperse the precipitate obtained in Step 5 in 5 mL of this Tris solution, and stir magnetically (at a speed of 300 rpm) to ensure uniform dispersion of the precipitate; slowly add 2 mL of a 0.5 mg / mL dopamine hydrochloride solution, and expose to air at 25 °C for 24 h with stirring.

[0097] Step 7: Centrifuge the mixture obtained in Step 6 at 8000 rpm for 3 min, discard the supernatant, wash the precipitate 3 times with deionized water, and finally disperse the precipitate in 2 mL of deionized water to obtain a responsive colloidal nanorobot suspension with a concentration of 0.5 mg / mL, and store it at 4℃.

[0098] Figure 5 These are optical microscope images of the micron-scale responsive colloidal robot prepared in Specific Example 2, from... Figure 5 As can be seen, the nanorobots prepared by this invention have a spherical structure and a diameter of less than 10 μm.

[0099] Specific Example 3: This example provides a method for fabricating a pulsed laser-responsive colloidal robot with a diameter of approximately 50 micrometers. The specific steps are as follows:

[0100] Step 1: Prepare a 0.1% (w / w) aqueous solution of Pronic F-127 for later use;

[0101] Step 2: Measure 100 μL of perfluorohexane and add it to 3 mL of the Pronic F-127 aqueous solution prepared in Step 1. Emulsify the solution by ultrasonication at 20 kHz and 30 W at 25 °C for 0.5 min to form a perfluorohexane droplet suspension.

[0102] Step 3: Centrifuge the suspension obtained in Step 2 at 1000 rpm for 3 min, discard the supernatant and collect the bottom precipitate; wash the precipitate twice with deionized water, centrifuging at 1000 rpm for 3 min after each wash to obtain purified perfluorohexane droplets;

[0103] Step 4: Disperse the perfluorocarbon droplets obtained in Step 3 in 6 mL of deionized water and stir magnetically (at 500 rpm) to ensure uniform dispersion of the droplets; add 0.5 mL of 10 mM tetrachloropalladium acid solution and stir at room temperature for 2 h; then add 0.5 mL of 0.1 mg / mL ascorbic acid solution and continue stirring at room temperature for 2 h.

[0104] Step 5: Centrifuge the mixture obtained in Step 4 at 1000 rpm for 3 min, discard the supernatant, wash the precipitate twice with deionized water to obtain perfluorocarbon droplets for assembling Pd NPs;

[0105] Step 6: Prepare a 10 mM Tris solution (pH=8.5), disperse the precipitate obtained in Step 5 in 5 mL of this Tris solution, and stir magnetically (at a speed of 300 rpm) to ensure uniform dispersion of the precipitate; slowly add 2 mL of a 0.5 mg / mL dopamine hydrochloride solution, and expose to air at 25 °C for 24 h with stirring.

[0106] Step 7: Centrifuge the mixture obtained in Step 6 at 1000 rpm for 3 min, discard the supernatant, wash the precipitate 3 times with deionized water, and finally disperse the precipitate in 2 mL of deionized water to obtain a responsive colloidal nanorobot suspension with a concentration of 0.5 mg / mL, and store it at 4℃.

[0107] Figure 6 These are optical microscope images of the micron-scale responsive colloidal robot prepared in Specific Example 3, from... Figure 6 It can be seen that the nanorobots prepared by this invention have a spherical structure with a diameter of about 50 μm.

[0108] Specific Implementation Example 4: This embodiment provides an example of recording and measuring the stepping motion of a micro / nano robot under pulsed laser drive using an optical microscope. Specifically:

[0109] The micro-nano robots in Specific Embodiment 2 and Specific Embodiment 3 were dispersed in water, and about 500 μL of the micro-nano robot suspension was dropped onto a glass slide using a pipette or Pasteur pipette.

[0110] The slide carrying the micro-nano robot was placed under an inverted optical microscope, and a CCD camera was connected to a computer. The focus was adjusted to make the image clear and to position it in the right place.

[0111] Set the pulsed laser parameters, irradiate the micro-nano robot from the side of the microscope, and simultaneously acquire video images for more than 1 minute;

[0112] Image analysis software was used to analyze the micro- and nanorobots. A Cartesian coordinate system was established with the lower left corner of the video as the origin. The coordinate changes of 15 micro- and nanorobots were recorded, and their motion trajectories were analyzed and plotted.

[0113] Figure 7 The motion trajectories of 15 micro-nano robots with a size of less than 10 μm prepared by the method of specific embodiment 2 of the present invention were obtained without the application of pulsed laser driving. Specifically, the motion of the micro-nano robots in the microscope field of view was collected in a natural state without the application of pulsed laser, 15 of which were selected and their motion trajectories were plotted using image analysis software. Figure 7 The results showed that without pulsed laser stimulation, the movement range of the nanorobots was significantly limited, and the micro-nanorobots mainly exhibited Brownian motion with short movement distances.

[0114] Figure 8 The motion trajectories of 15 micro-nano robots with a size less than 10 μm, prepared by the method of Specific Embodiment 2 of the present invention, were obtained when driven by a 2W pulsed laser. A 2W pulsed laser was applied, and the motion of the micro-nano robots in the microscope field of view was acquired. Fifteen of these micro-nano robots were selected, and their motion trajectories were plotted using image analysis software. Figure 8 The results showed that when stimulated by pulsed laser, the motion trajectory of the nanorobots followed the pulsed laser.

[0115] Figure 9 The motion trajectories of 15 micro-nano robots with a size less than 10 μm, prepared by the method of Specific Embodiment 2 of the present invention, were obtained when driven by a 3W pulsed laser. A 3W pulsed laser was applied, and the motion of the micro-nano robots in the microscope field of view was acquired. Fifteen of these micro-nano robots were selected, and their motion trajectories were plotted using image analysis software. Figure 9 The results showed that when stimulated by pulsed laser, the motion trajectory of the nanorobots followed the pulsed laser.

[0116] Figure 10 The present invention describes the motion trajectories of 15 microrobots, each approximately 50 μm in size, prepared using the method described in Specific Embodiment 3 of the present invention, under 2W pulsed laser power. Specifically, a 2W pulsed laser was applied, and the motion of the microrobots in the microscope field of view was collected. Fifteen of these microrobots were selected, and their motion trajectories were plotted using image analysis software. Figure 10 The results showed that the micro-nano robots followed the laser-guided movement when stimulated by pulsed laser. However, due to the relatively large size of the micro-nano robots in specific embodiment 2, they remained stationary in the untreated state and did not exhibit similar behavior. Figure 7 The specific embodiment 2 shown in the figure is Brownian motion, so no motion trajectory is recorded.

[0117] Figure 11 To be based on respectively Figure 7 (Red, 10μm micro-nano robots without pulsed laser irradiation) Figure 8 (Green, 10μm micro-nano robots applying 2W pulsed laser) Figure 9 (Purple, 10μm micro-nano robots applying 3W pulsed laser) Figure 10 (Blue, 50μm micro / nano robot subjected to a 2W pulsed laser) The mean square displacement (MSD) of each group calculated using optical microscopy to record the motion trajectory of the robot in the image (blue, 50μm micro / nano robot with a 2W pulsed laser). From... Figure 11 It can be seen that the mean square displacement increases with the increase of pulsed laser power.

[0118] Figure 12 and Figure 13 According to Figure 11 The diffusion coefficient and velocity data of each group were calculated from the MSD data. Figure 12 and Figure 13 Group 1 consists of 10 μm micro / nano robots that were not irradiated by pulsed laser, with an average diffusion coefficient of 3.07 μm. 2 The velocity of Group 1 was 4.30 μm / s; Group 2 consisted of 10 μm micro / nano robots with a 2W pulsed laser, and the average diffusion coefficient was 7.31 μm. 2 The velocity was 6.62 μm / s; Group 3 consisted of 10 μm micro / nano robots + 3W pulsed laser, with an average diffusion coefficient of 10.19 μm. 2 The velocity was 7.82 μm / s; Group 4 consisted of 50 μm micro / nano robots + 2W pulsed laser, with an average diffusion coefficient of 14.79 μm. 2 / s, with a velocity of 9.42μm / s. Figure 12 The results show that the diffusion coefficient of the target nanorobots increases significantly with increasing pulsed laser power, and the larger diameter nanorobots move faster. This indicates that pulsed laser irradiation can effectively enhance the motion activity of micro- and nanorobots, and the higher the laser power, the more significant the improvement in their motion ability. Furthermore, under the same laser power excitation, 50 μm micro- and nanorobots exhibit stronger motion dynamics characteristics compared to 10 μm microrobots, making them more likely to achieve efficient diffusion in the environment. Figure 13 The results show that using pulsed lasers to drive the movement of this nanorobot has the potential to overcome physical barriers.

[0119] Specific Implementation Example 5: This embodiment provides an example of determining the motion speed of a micro / nano robot driven by a pulsed laser using a macroscopic measurement method, specifically:

[0120] Take about 3 mL of the 10 μm micro-nano robot suspension prepared in Specific Example 2 and add it to a quartz cuvette with an inner diameter of 10 mm × 10 mm × 40 mm. Let the cuvette stand and allow the micro-nano robots to naturally settle to the bottom of the cuvette to form a uniform robot precipitation layer.

[0121] Fix the quartz cuvette loaded with the robot's deposited layer, and adjust the laser output port to be vertically aligned with the center area of ​​the bottom of the cuvette.

[0122] Video recording was performed on the cuvette, and a pulsed laser was simultaneously activated to vertically illuminate the robot's deposit layer from the bottom of the cuvette, resulting in a macroscopic video of the robot's motion, and the motion speed was calculated.

[0123] Figure 14 This paper presents the macroscopic motion of a 10 μm micro / nano robot under 2W pulsed laser drive, recorded using a macroscopic measurement method. Experimental results show that when the laser power is 2W, the average movement distance of the micro / nano robot after 5 seconds of application is 25.79 mm, corresponding to an average speed of 5158 μm / s. The results demonstrate that increasing the pulsed laser power can significantly increase the movement speed of the micro / nano robot, and the speed data obtained by this method can intuitively reflect the robot's motion capability at the macroscopic scale.

[0124] Specific Implementation Example 6: This embodiment provides an example of how micro-nano robots enhance the penetration of physical barriers under pulsed laser drive, specifically as follows:

[0125] The nanorobots prepared in Specific Example 1 were dispersed in PBS and fluorescently labeled with the near-infrared fluorescent dye indocyanine green.

[0126] 100 μL of fluorescently labeled nanorobots were injected into a GL261 mouse subcutaneous tumor animal model via tail vein injection. Two hours later, images of their distribution in vivo were acquired using an in vivo fluorescence imaging device.

[0127] The pulsed laser parameters were set, and the mouse tumor site was irradiated with pulsed laser for 5 minutes. The distribution of the fluorescently labeled nanorobots was collected using an in vivo fluorescence imager.

[0128] Figure 15 The figures presented show the in vivo distribution of nanorobots with a size of less than 0.1 μm, prepared using the method of Specific Example 1 of this invention, after being labeled with indocyanine green and injected into a GL261 mouse subcutaneous tumor animal model and subjected to pulsed laser treatment. Figure 15 In the diagram, (a) represents the bulk distribution state before the application of pulsed laser light. Figure 15(b) shows the in vivo distribution after the application of pulsed laser. The results show that although the nanorobots have accumulated to some extent around the tumor 2 hours after being injected into mice, the degree of accumulation in the tumor tissue is low. However, after irradiation with pulsed laser, the accumulation in the tumor tissue increases significantly. This indicates that pulsed laser can drive the nanorobots to move in a directional manner, thereby overcoming the physical barrier of the tumor and achieving rapid accumulation in the tumor site.

[0129] It should be noted that, in this document, the terms "comprising," "including," or any other variations thereof are intended to cover non-exclusive inclusion, such that a process, method, article, or apparatus that comprises a list of elements includes not only those elements but also other elements not expressly listed, or elements inherent to such a process, method, article, or apparatus. Unless otherwise specified, an element defined by the phrase "comprising one..." does not exclude the presence of other identical elements in the process, method, article, or apparatus that includes that element.

[0130] The embodiments of the present invention have been described above with reference to the accompanying drawings. However, the present invention is not limited to the specific embodiments described above. The specific embodiments described above are merely illustrative and not restrictive. Those skilled in the art can make many other forms under the guidance of the present invention without departing from the spirit and scope of the claims. All of these forms are within the protection scope of the present invention.

Claims

1. A pulsed laser-responsive colloidal micro / nano robot, characterized in that, The micro-nano robot has a spherical structure and includes a core layer and a functional layer from the inside out. The functional layer covers the core layer. The core layer is a thermally responsive phase change material, and the functional layer is a noble metal nanomaterial. The noble metal nanomaterial in the functional layer absorbs and converts near-infrared pulsed laser light into thermal energy, causing the core layer to undergo a phase change, which drives the micro-nano robot to achieve stepping motion and penetrate physical barriers. The core layer comprises liquid perfluorocarbon, and the functional layer comprises palladium nanoparticles. The functional layer absorbs near-infrared pulsed laser light and converts the light energy into heat energy, thereby triggering the cavitation phase transition of the liquid perfluorocarbon in the core layer, resulting in dynamic configuration transformation, stepping motion, and penetration of physical barriers. The micro-nano robot also includes a modification layer located on the outer surface of the functional layer, and the modification layer is polydopamine. The liquid perfluorocarbon is perfluorohexane.

2. The pulsed laser-responsive colloidal micro / nano robot according to claim 1, characterized in that, The perfluorohexane was prepared by high-energy ultrasonic mechanical emulsification to form uniform droplets with a particle size of 0.05-50 μm, thereby making the initial particle size of the micro-nano robot 0.05-50 μm.

3. The pulsed laser-responsive colloidal micro / nano robot according to claim 1, characterized in that, The palladium nanoparticles were prepared by reducing tetrachloropalladium acid with ascorbic acid, and the particle size was 5-60 nm.

4. The pulsed laser-responsive colloidal micro / nano robot according to claim 2, characterized in that, The polydopamine is formed by dispersing dopamine hydrochloride in an alkaline solution with a pH of 8.5 and then exposing it to air for oxidative polymerization; the alkaline solution is one of tris(hydroxymethyl)aminomethane buffer solution, sodium hydroxide solution, and phosphate buffer solution.

5. A method for preparing pulsed laser-responsive colloidal micro / nano robots as described in any one of claims 1-4, characterized in that, Includes the following steps: Preparation of the S1 micro / nano robot core layer: 20-500 μL of perfluorohexane was dispersed in 1-5 mL of a nonionic copolymer solution with a mass concentration of 0.1-0.5%, emulsified by ultrasound, and collected by centrifugation to obtain perfluorocarbon droplets; Assembly of the S2 micro / nano robot functional layer: Disperse perfluorocarbon droplets in 2-15 mL of deionized water to a volume concentration of 2-10%, add 0.5-1.5 mL of 10 mM tetrachloropalladic acid, and stir for 2-12 h; then add 0.2-1 mL of 0.1 mg / mL ascorbic acid solution, react for 2-4 h, collect by centrifugation, and obtain perfluorocarbon droplets with assembled palladium nanoparticles, thus obtaining the micro / nano robot; Assembly of the S3 micro / nanorobot modification layer: The assembled palladium nanoparticles were dispersed in 5-25 mL of 10 mM Tris solution at pH 8.5, and 0.5-5 mL of 0.5 mg / mL dopamine hydrochloride solution was added. The mixture was then exposed to air at 25°C and stirred for 24 h. After centrifugation, the assembled and modified micro / nanorobots were obtained.

6. The application of the pulsed laser-responsive colloidal micro / nanorobot as described in any one of claims 1-5 in the preparation of a drug delivery system.

7. The application according to claim 6, characterized in that, The drug delivery system includes a carrier for loading drug molecules to achieve targeted delivery, or a carrier for in vitro photodynamic therapy drugs, or a carrier for loading photocatalysts in photocatalytic therapy.

8. The application according to claim 7, characterized in that, The applications include fabricating the micro-nanorobot into a targeted carrier for the treatment of stroke or malignant brain tumors.

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