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CN-121971663-A - Radioactive hydrogel, preparation method and application thereof, and radioactive tumor treatment application

CN121971663ACN 121971663 ACN121971663 ACN 121971663ACN-121971663-A

Abstract

A radioactive hydrogel, its preparation method and application, and radioactive tumor therapeutic application, uses chitosan as matrix, and constructs three-dimensional network by cross-linking with genipin, and can realize stable loading and slow release of radionuclide simultaneously; the self antibacterial and adhesive properties of the medical patch can reduce infection risk and ensure application fixation, so that a safe, effective and simple-to-operate local treatment platform is provided, the prepared application can be directly placed on a tumor bed after surgical excision, beta or alpha rays released by radionuclides are precisely and continuously acted on the area most likely to remain tumor cells, the fixed point clearance is realized, and the hydrogel can continuously release radiation with low dose rate unlike the traditional external irradiation radiotherapy. The mode has stronger biological effect (such as inhibition of re-proliferation) on tumor cells, can overcome the radiosensitivity difference of different phases of cell cycle, has more thorough killing effect, and the chitosan has proved to have certain antibacterial, tumor cell growth inhibition and immunoregulatory activity. It can produce synergistic effect with radionuclide to construct a microenvironment unfavorable for tumor cell survival and recurrence.

Inventors

  • LIU YANG
  • YU GUANGDONG
  • CHEN LEI
  • LI BIN
  • LI YONG

Assignees

  • 国科温州科技发展有限公司

Dates

Publication Date
20260505
Application Date
20251222

Claims (10)

  1. 1. The radioactive hydrogel is characterized by comprising chitosan-genipin three-dimensional network hydrogel entrapped ultra-small gold nanoparticles and radioactive elements, wherein the radioactive elements are labeled by the ultra-small gold nanoparticles.
  2. 2. The radioactive hydrogel of claim 1, wherein the radioactive element is one of yttrium-90 ( 90 Y), iodine-131 ( 131 I), astatine-211 ( 211 At), lutetium-177 ( 177 Lu), strontium-89 ( 89 Sr) or lanthanum-166 ( 166 Ho).
  3. 3. The radioactive hydrogel of claim 1, wherein the ultra-small gold nanoparticles are PEG-modified ultra-small gold nanoparticles.
  4. 4. A method of preparing a radioactive hydrogel according to claim 1, comprising the steps of: (1) Pre-cooling deionized water at 4 ℃, adding chloroauric acid and potassium carbonate, then adding sodium citrate and sodium borohydride, changing the color into red orange, then adding excessive sulfhydryl PEG after ice bath stirring, and heating and curing to obtain PEG modified ultra-small gold nanoparticles AuNPs; (2) Adding PBS buffer solution with pH of 7.4 into the ultra-small gold nanoparticles, adding the radioactive element solution, vibrating at a constant temperature of 37 ℃, and performing ultrafiltration purification to obtain AuNPs for marking the radioactive elements; (3) The preparation method of the genipin-chitosan hydrogel comprises the steps of adding acetic acid into chitosan according to the proportion of 1 g/100 mL, stirring at room temperature to obtain colorless transparent chitosan solution, dissolving genipin powder in ultrapure water, oscillating until the genipin powder is completely dissolved, uniformly mixing the genipin aqueous solution and the ultra-small gold nanoparticles, slowly dripping the genipin solution into the chitosan solution under the stirring condition, continuously stirring to ensure uniform mixing, then injecting the mixed solution into a mold, standing to complete crosslinking, enabling genipin and chitosan to form a blue-green gel network, and embedding the ultra-small gold nanoparticles in situ, thus obtaining the uniform genipin-chitosan hydrogel for encapsulating the ultra-small gold nanoparticles.
  5. 5. The method according to claim 4, further comprising the steps of directly filling the crosslinked radioactive hydrogel into a dialysis bag, draining the air, clamping the bag opening, adding the radioactive hydrogel into ultrapure water, rapidly dialyzing the radioactive hydrogel at a volume ratio of 1:200 for 6h, changing water every 1:1 h, continuously standing and dialyzing the radioactive hydrogel for 48 h after changing water every 1:500, changing water every 6h, measuring absorbance of the external liquid for 280 nm to be less than 0.01, balancing the radioactive hydrogel for 6h, taking out the gel, lightly filtering out surface moisture, and preserving the gel at 4 ℃ to finish the purification. .
  6. 6. The method of claim 5, wherein the dialysis bag is a 3.5 kDa dialysis bag.
  7. 7. The method according to claim 4, wherein the mass ratio of the excess sulfhydryl PEG to chloroauric acid in the step (1) is greater than 1.
  8. 8. Use of the radioactive hydrogel of claim 1 for the preparation of a material for the radiation treatment of tumors.
  9. 9. The use of claim 8, wherein the radiation therapy tumor material is a radiopharmaceutical application.
  10. 10. The radioactive tumor treatment application is characterized by being prepared from the radioactive hydrogel of claim 1, wherein the radioactive hydrogel is chitosan-genipin three-dimensional network hydrogel loaded with ultra-small gold nanoparticles AuNPs of 131I, and 120 mu Ci 131I is stably loaded per mu g of AuNPs.

Description

Radioactive hydrogel, preparation method and application thereof, and radioactive tumor treatment application Technical Field The invention relates to the technical field of medical equipment, in particular to radioactive hydrogel, a preparation method and application thereof and radioactive tumor treatment application. Background Tumors are one of the main diseases causing death worldwide, wherein the incidence and death rate of malignant solid tumors such as melanoma, liver cancer and the like rise year by year. For these tumors, various means such as surgical excision, chemotherapy, radiotherapy, targeted therapy and immunotherapy are commonly used in clinic. However, conventional radiation therapy (External Beam Radiation Therapy, EBRT) has limitations in the treatment process, such as difficulty in precise control of the radiation dose distribution, radiation damage to surrounding normal tissues, and the need for multiple exposure of the patient to radiation therapy, which increases medical costs and adverse reactions. Therefore, it is of great clinical value to develop a radiotherapy method capable of stably releasing radioactive energy at a tumor part and reducing normal tissue damage. The ideal local radiotherapy carrier can simultaneously meet the requirements that ① can be in-situ glued and firmly adhered to a tumor bed to avoid displacement, ② three-dimensional network can controllably release radionuclide to realize continuous, low-dose and accurate irradiation, ③ is biodegradable and does not need secondary extraction, ④ has antibacterial and hemostatic functions, and reduces postoperative infection and bleeding risks. Disclosure of Invention In order to solve the defects and shortcomings of the prior art, the invention provides the radioactive hydrogel, the preparation method and application thereof and the radioactive tumor treatment application, wherein chitosan is used as a matrix, and the chitosan is crosslinked with genipin to construct a three-dimensional network, so that stable loading and slow release of radionuclide can be synchronously realized, and the antibacterial and adhesive properties of the radioactive hydrogel can reduce infection risks and ensure application fixation, thereby providing a safe, effective and simple-to-operate local treatment platform. The technical scheme includes that the radioactive hydrogel consists of chitosan-genipin three-dimensional network hydrogel coated with ultra-small gold nanoparticles and radioactive elements, wherein the radioactive elements are marked by the ultra-small gold nanoparticles. The radioactive element is one of yttrium-90 (90 Y), iodine-131 (131 I), astatine-211 (211 At), lutetium-177 (177 Lu), strontium-89 (89 Sr) or lanthanum-166 (166 Ho). The ultra-small gold nanoparticles are PEG-modified ultra-small gold nanoparticles. A method for preparing a radioactive hydrogel, comprising the steps of: (1) Pre-cooling deionized water at 4 ℃, adding chloroauric acid and potassium carbonate, then adding sodium citrate and sodium borohydride, changing the color into red orange, then adding excessive sulfhydryl PEG after ice bath stirring, and heating and curing to obtain PEG modified ultra-small gold nanoparticles AuNPs; (2) The method comprises the steps of (1) marking radioactive elements by using ultra-small gold nanoparticles, namely, lightly blowing ultra-small gold nanoparticles AuNPs with PBS (phosphate buffer solution) with pH of 7.4 to disperse the ultra-small gold nanoparticles AuNPs, adding a carrier-free radioactive element solution, supplementing PBS, swirling the solution, placing the solution at a constant temperature of 37 ℃ for shaking, and incubating the solution in a dark place to obtain the AuNPs loaded with the radioactive elements; (3) The preparation method of the genipin-chitosan hydrogel comprises the steps of adding acetic acid into chitosan according to the proportion of 1 g/100 mL, stirring at room temperature to obtain colorless transparent chitosan solution, dissolving genipin powder in ultrapure water, oscillating until the genipin powder is completely dissolved, uniformly mixing the genipin aqueous solution and the ultra-small gold nanoparticles, slowly dripping the genipin solution into the chitosan solution under the stirring condition, continuously stirring to ensure uniform mixing, then injecting the mixed solution into a mold, standing to complete crosslinking, enabling genipin and chitosan to form a blue-green gel network, and embedding the ultra-small gold nanoparticles in situ, thus obtaining the uniform genipin-chitosan hydrogel for encapsulating the ultra-small gold nanoparticles. The method further comprises the steps of purifying the radioactive hydrogel, namely directly filling the crosslinked radioactive hydrogel into a dialysis bag, exhausting air, clamping the bag opening, adding the radioactive hydrogel into ultrapure water, rapidly dialyzing the radioactive hydrogel into the ultrapure water ac