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CN-121987833-A - Electric immune hydrogel and preparation method and application thereof

CN121987833ACN 121987833 ACN121987833 ACN 121987833ACN-121987833-A

Abstract

The invention discloses an electro-immune hydrogel and a preparation method and application thereof, belonging to the crossing field of biomedical engineering and tumor treatment. The electro-immune hydrogel (APC-CUR@eigel) is composed of a sodium alginate framework, an in-situ polymerized polypyrrole conductive network, and loaded calcium carbonate and curcumin, and has a three-dimensional porous structure and good conductivity. The prepared electric immune hydrogel is molded in situ after intratumoral injection, so that the electric conductivity uniformity of tumor tissues can be remarkably improved, the PFA electric field distribution is optimized, the ablation blind area is reduced, meanwhile, ca 2+ is slowly released, the activity of a calcium pump is inhibited by combining with curcumin, the calcium overload is induced to trigger the scorching, and a large amount of released cytokines can effectively activate anti-tumor immune response, remodel immune microenvironment and promote a far-distance effect. The electro-immune hydrogel prepared by the invention has biological safety, degradability and clinical compatibility.

Inventors

  • Jiang tianan
  • XIE LITING
  • XU FAN

Assignees

  • 浙江大学医学院附属第一医院(浙江省第一医院)

Dates

Publication Date
20260508
Application Date
20260206

Claims (10)

  1. 1. An electro-immune hydrogel, which is characterized by being of a three-dimensional porous network structure and comprising the following components: The slow-release calcium ion calcium source comprises sodium alginate Alg, in-situ polymerized polypyrrole PPy, a slow-release calcium ion Ca 2+ system composed of an exogenous calcium source and D-glucose-delta lactone GDL and curcumin, wherein the molar ratio of the components is Alg to PPy to Ca 2+ =1 to 1-3 to 1-2 in the exogenous calcium source.
  2. 2. The electro-immune hydrogel of claim 1, wherein the exogenous calcium source is one of calcium chloride, calcium gluconate, calcium sulfate, calcium acetate and calcium hydroxide, preferably calcium carbonate.
  3. 3. The electro-immune hydrogel of claim 1, wherein the slow-release calcium ion Ca 2+ system consists of an exogenous calcium source and D-glucose-delta lactone GDL in a molar ratio of 1:2.
  4. 4. The electro-immune hydrogel of claim 1, wherein the molar ratio of curcumin to calcium ions is 1:10.
  5. 5. The electro-immune hydrogel of claim 1, wherein the molar ratio of Alg: PPy to Ca 2+ in the exogenous calcium source is preferably 1:1.5:1.5.
  6. 6. A method of preparing an electro-immune hydrogel according to any one of claims 1 to 5, comprising the steps of: (1) Preparing sodium alginate solution with the mass concentration of 2%; (2) Respectively adding pyrrole monomer with the molar equivalent of 1.0-3.0 times of sodium alginate, sodium persulfate with the molar equivalent of 2.5 times of pyrrole and sodium bicarbonate with the molar equivalent of 4.0 times of pyrrole into the solution for in-situ polymerization, and stirring for 4 hours at 1000rpm in ice bath or room temperature; (3) Placing the solution in a dialysis bag for dialysis and purification 48 h; (4) After the dialysis is finished, adding 1.0 to 3.0 times of sodium alginate molar equivalent of an exogenous calcium source/GDL slow release system and curcumin into the dialysis solution, and stirring the mixture by 1000 rpm to 1 min to prepare the electro-immune hydrogel.
  7. 7. The method of claim 6, wherein in step (2), pyrrole monomer is replaced with aniline, phenyl ether, thiophene, acetylene.
  8. 8. The method of claim 6, wherein the dialysis bag has a molecular weight cut-off of 5000 KD in step (3).
  9. 9. The method of claim 6, wherein in step (4), the molar ratio of exogenous calcium source to D-glucose-delta-lactone GDL is 1:2 and the molar ratio of curcumin to calcium ion is 1:10.
  10. 10. Use of an electro-immune hydrogel according to any one of claims 1-5 in the preparation of a formulation for enhancing the effect of pulsed electric field ablation on tumors.

Description

Electric immune hydrogel and preparation method and application thereof Technical Field The invention belongs to the crossing field of biomedical engineering and tumor treatment, and relates to an electro-immune hydrogel and a preparation method and application thereof. Background Pancreatic ductal adenocarcinomas are a highly malignant tumor, accounting for over 90% of pancreatic carcinomas, with highly invasive and early metastatic properties, and how to effectively treat pancreatic ductal adenocarcinomas remains an important challenge in the current medical field. The traditional treatment means (operation, chemotherapy and radiotherapy) have limited effect on advanced patients, and the survival rate of 5 years is less than 10 percent. There is a great need to explore new methods of treating pancreatic cancer. The pulse electric field ablation (PFA) is a non-heat-dependent ablation means, and the high-voltage pulse electric field acts on cell membranes, so that important structures around pancreas can be effectively protected, the influence of a heat sink effect is avoided, and the method has unique advantages in the treatment of pancreatic duct adenocarcinoma. However, the pulse electric field ablation technology has the specific limitations that the ablation is not thorough due to uneven electric field distribution and low conductivity of tumor tissues, and the immune activation is insufficient, namely tumor cells in a low field intensity region remain, the related molecular modes of injury cannot be effectively released, the immune response of an organism cannot be activated and effectively maintained, and finally the tumor recurrence and metastasis can be possibly caused. At present, the method for compensating the partial electric field shortage of the pulsed electric field ablation technology by enhancing the electric conduction performance is a common method, so that the selection of the conductive material is important. Research shows that the conductive polymer material such as polypyrrole can effectively enhance the conductivity of tissues around tumors. But the single conductive polymer material has simple structure and single function, has shorter residence time in the tumor tissue gap, and can not effectively optimize and regulate the microenvironment around the tumor for a long time. Apoptosis, also known as inflammatory programmed cell death, is a ubiquitous mechanism of cell death that stimulates the body to produce an inflammatory response and activate the immune system. Ca 2+ has been identified as a potent inducer of GSDME-mediated apoptosis, but calcium ion solutions have not only high systemic toxicity, uncontrollable local concentrations, and low bioavailability if used by direct injection. Therefore, the development of the electric immune hydrogel capable of compounding the conductive high molecular polymer and the metal calcium ions can enable the electric immune hydrogel to regulate and control the electric microenvironment and the immune microenvironment of tumor tissues for a long time, and the electric immune hydrogel has very good prospect and vital importance for optimizing the clinical curative effect of pulsed electric field ablation. Disclosure of Invention In order to overcome the problems in the prior art, the invention provides an electro-immune hydrogel and a preparation method and application thereof, and aims to optimize tumor tissue microecology and enhance the ablation effect of pulsed electric field ablation. In order to achieve the above purpose, the invention adopts the following technical scheme: In a first aspect, the present invention provides an electro-immune hydrogel; The hydrogel is of a three-dimensional porous network structure, comprises an ionic gel matrix formed by a sodium alginate framework, an in-situ polymerization embedded conductive polypyrrole chain segment, a slow-release calcium ion Ca2+ system formed by an exogenous calcium source and D-glucose-delta lactone GDL according to a molar ratio of 1:2, and embedded functional micromolecular curcumin, wherein the molar ratio of the curcumin to the calcium ion is 1:10, and has the effect of regulating and controlling the activity of a calcium channel, and the molar mass ratio of the components is Alg: PPy: ca 2+ = 1:1-3:1-2 in the exogenous calcium source. Preferably, the exogenous calcium source is one of calcium chloride, calcium gluconate, calcium sulfate, calcium acetate and calcium hydroxide, and more preferably calcium carbonate. Preferably, the mole ratio of Alg to PPy to Ca 2+ in the exogenous calcium source is preferably 1:1.5:1.5. In a second aspect, the invention provides a method for preparing the electro-immune hydrogel, which comprises the following steps: s1, adding sodium alginate (1.00 g) into 50mL water, stirring for 2h to completely dissolve alginic acid, and preparing 2% alginate solution; S2, respectively adding pyrrole (the molar equivalent is 1.0-3.0 times of sodium alginate