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CN-122005792-A - Preparation method for constructing light-driven nanomotor and application of light-driven nanomotor in tumor treatment

CN122005792ACN 122005792 ACN122005792 ACN 122005792ACN-122005792-A

Abstract

The invention discloses a light-driven CeVO 4 /Ag 2 S redox nano shuttle machine and a preparation method and application thereof, and belongs to the technical field of nano biological medicines. The nano shuttle machine is in a core-shell structure and comprises a cerium vanadate (CeVO 4 ) core with triple bionic catalytic activities of peroxidase, catalase and glutathione peroxidase, a mesoporous silica shell layer coated on the outer side of the core, and silver sulfide (Ag 2 S) photo-thermal nano particles modified on the shell layer. Under the irradiation of initial near infrared light, ag 2 S on the surface is used as a photo-thermal engine to generate a local temperature gradient to drive a nano shuttle machine to generate active thermophoresis propelling force, so that the passive diffusion barrier is broken through to realize deep penetration of tumor tissues. The penetrated CeVO 4 core can efficiently utilize abundant endogenous substrates in the tumor microenvironment to carry out continuous cascade catalysis. The invention successfully constructs a closed loop system coupling thermophoresis propulsion and self-amplification catalysis, gets rid of the dependence of the traditional nano enzyme on continuous external energy input, and realizes long-acting and autonomous treatment for deep tumors.

Inventors

  • SUN TIEDONG
  • LIU XIANGWEI
  • CHEN CHUNXIA

Assignees

  • 东北林业大学

Dates

Publication Date
20260512
Application Date
20260302

Claims (7)

  1. 1. A preparation method for constructing an optical drive nano motor and application thereof in tumor treatment are characterized in that the method comprises the following steps: Step one, synthesis of cerium vanadate nanorods Cerium nitrate and EDTA were completely dissolved in deionized water with stirring at 80 ℃, and a sodium metavanadate solution was added thereto. The pH of the mixed solution was then adjusted to 10.0 with sodium hydroxide adjustment. Finally the suspension was placed in an autoclave for a treatment of 24 hours at 180 ℃. After cooling to room temperature, centrifugally collecting the precipitate, and washing with deionized water and ethanol for several times; step two, synthesis of PEI modified Ag2S nanodots Polyethyleneimine (1.25 mM) was dissolved in deionized water (75 mL) under a stream of argon followed by the addition of silver nitrate (0.25 mM). The pH of the solution was adjusted to 10.5 with sodium hydroxide (2.0 mM). Thioacetamide solution was added to the solution and silver ion solution was slowly added with vigorous stirring. Finally, the reaction mixture is kept at 70 ℃ for 1 hour; step three, synthesis of CAP nanomotor Carboxylated CVO@SiO2 was dispersed in DMF by sonication with magnetic stirring. EDC and NHS were added to the suspension to activate the carboxyl groups. Subsequently, a DMF solution of PEI-Ag2S was added to the activated suspension and stirred vigorously for 24 hours. The resulting solid product was collected by centrifugation, washed three times with DMF and ethanol each, and then dried. Finally, the resulting solid was redispersed in ethanol and PVP was added to modify its surface. The final CAP nanomotor was collected by centrifugation, washed with ethanol and dried for later use.
  2. 2. The nano-shuttle of claim 1, wherein the cerium vanadate (CeVO 4 ) core contains a dual redox couple of Ce 3+ /Ce 4+ and V 4+ /V 5+ .
  3. 3. The nano-shuttle machine according to claim 2, wherein the cerium vanadate (CeVO 4 ) core has three biomimetic catalytic activities of Peroxidase (POD), catalase (CAT) and glutathione peroxidase (GPx) simultaneously.
  4. 4. The nano-shuttle of claim 1, wherein the silver sulfide (Ag 2 S) nanoparticles have near infrared light thermal conversion properties, capable of generating a local temperature gradient under near infrared light irradiation, and driving the nano-shuttle to perform active thermophoresis propulsion.
  5. 5. A preparation method of a redox nano shuttle machine according to any one of claims 1-4 is characterized by comprising the following steps of (1) synthesizing cerium vanadate (CeVO 4 ) nano cores, (2) coating mesoporous silica (mSiO 2 ) on the surfaces of the CeVO 4 cores to obtain a CeVO 4 @mSiO 2 core-shell structure, and (3) growing or loading silver sulfide (Ag 2 S) nano particles on mesoporous shells of the CeVO 4 @mSiO 2 in situ to obtain the CeVO4/Ag2S redox nano shuttle machine.
  6. 6. Use of the redox nanoshutters according to any of claims 1 to 4 for the preparation of an anti-tumor drug or a tumor therapeutic formulation.
  7. 7. The application of the method according to claim 6, wherein the application mechanism is that the nano shuttle machine generates local temperature gradient drive thermophoresis propulsion through Ag 2 S under the initial near infrared light irradiation to penetrate through the deep layer of the tumor, and utilizes hydrogen peroxide and glutathione in the microenvironment of the tumor as substrates to perform continuous catalysis through triple enzyme activity of a CeVO 4 core to form a self-maintenance anti-tumor closed loop system without external continuous energy input.

Description

Preparation method for constructing light-driven nanomotor and application of light-driven nanomotor in tumor treatment Technical Field The invention relates to the technical field of nano medicine and biomedical materials, in particular to a CeVO 4/Ag2 S redox nano shuttle machine which is driven by light and has three-enzyme bionic catalytic activity and autonomous thermophoresis propulsion capability, a preparation method thereof and application thereof in deep tumor treatment. Background Cancer is a serious threat to global health and has the characteristics of high recurrence rate, distant metastasis, acquired drug resistance and the like. Although the conventional operation, radiotherapy and chemotherapy have wide application, the conventional operation, radiotherapy and chemotherapy often depend on repeated administration or continuous external energy input to cause serious systemic side effects, and the physiological barrier of deep tumor tissues is difficult to overcome effectively, so that the accumulation of medicines or energy in the deep tumor is insufficient, and the treatment effect is severely restricted. Nano-enzyme as an emerging therapeutic agent with enzyme mimetic properties exhibits great potential for use by virtue of its high stability, ease of functionalization and ability to regulate the tumor microenvironment. However, the clinical transformation is still limited by inherent defects of low catalysis efficiency under physiological conditions, limited penetration depth caused by blockage of compact tumor matrixes, incapacity of realizing autonomous treatment due to high dependence on exogenous substrates or continuous external stimulation, and the like. Although the use of endogenous substances such as high concentration hydrogen peroxide, glutathione and the like in the tumor microenvironment to drive catalytic reactions has become a research hotspot. And a material having a double redox pair represented by cerium vanadate (CeVO 4) shows excellent electron transfer ability, but a single material still faces the problems of unstable structure, narrow pH tolerance range and lack of self-sustaining activation mechanism, resulting in limited efficacy in deep tumors. Meanwhile, although photo-thermal therapy (PTT) is introduced to enhance the curative effect through the heat generation assistance of near infrared light, the prior strategy is limited to unidirectional heat promotion catalysis, and a mutual coupling mechanism of propulsion power and catalysis reaction cannot be established. Traditional photothermal therapy is inherently limited by the depth of tissue penetration of light and reliance on sustained illumination, making it difficult to achieve truly autonomous, long-lasting treatment in deep tumors. Therefore, developing a self-driven nanometer diagnosis and treatment platform which can be started by using short external stimulus, has the capability of actively crossing a diffusion barrier and can maintain long-acting catalytic circulation by using endogenous resources is a technical problem to be solved in the current tumor treatment field. Disclosure of Invention The invention aims to provide a light-driven CeVO4/Ag2S redox nano shuttle machine. The nano shuttle comprises cerium vanadate (CeVO 4) cores with redox activity and silver sulfide (Ag 2S) nano particles with photo-thermal capability. In order to achieve the above purpose, the technical scheme adopted by the invention is as follows: An optical-driven CeVO 4/Ag2 S redox nano shuttle with three-enzyme bionic catalytic activity and autonomous thermophoresis propulsion capability, a preparation method thereof and application thereof in deep tumor treatment. The preparation steps of the nano motor are as follows: Step one, synthesis of cerium vanadate nanorods Cerium nitrate and EDTA were completely dissolved in deionized water with stirring at 80 ℃, and a sodium metavanadate solution was added thereto. The pH of the mixed solution was then adjusted to 10.0 with sodium hydroxide adjustment. Finally the suspension was placed in an autoclave for a treatment of 24 hours at 180 ℃. After cooling to room temperature, the precipitate was collected by centrifugation and washed several times with deionized water and ethanol. Step two, synthesis of PEI modified Ag 2 S nano-dots Polyethyleneimine (1.25 mM) was dissolved in deionized water (75 mL) under a stream of argon followed by the addition of silver nitrate (0.25 mM). The pH of the solution was adjusted to 10.5 with sodium hydroxide (2.0 mM). Thioacetamide solution was added to the solution and silver ion solution was slowly added with vigorous stirring. The reaction mixture was finally maintained at 70 ℃ for 1 hour. Step three, synthesis of CAP nanomotor Carboxylated CVO@SiO 2 was dispersed in DMF by ultrasound under magnetic stirring. EDC and NHS were added to the suspension to activate the carboxyl groups. Subsequently, a solution of PEI-Ag 2 S in DMF was added to the act