CN-116474159-B - Constant-temperature photo-thermal system and application thereof

CN116474159BCN 116474159 BCN116474159 BCN 116474159BCN-116474159-B

Abstract

The invention relates to a constant temperature photo-thermal system and application thereof, which comprises the steps of obtaining near infrared thermal molecules through one-step Knoevenagel condensation, preparing near infrared thermal nanoparticles through a nano precipitation method by utilizing amphiphilic polymers, adding two monomers of N-isopropyl acrylamide and acrylamide through a free radical polymerization method, adding an initiator potassium persulfate and a cross-linking agent N, N-methylene bisacrylamide, fully mixing uniformly, polymerizing at room temperature to obtain poly (N-isopropyl acrylamide-acrylamide) hydrogel, dripping the near infrared thermal nanoparticles on an infected wound, and applying the poly (N-isopropyl acrylamide-acrylamide) hydrogel on the infected wound to realize constant temperature wound healing under the irradiation of near infrared laser. The constant-temperature photo-thermal system based on the poly (N-isopropyl acrylamide-acrylamide) hydrogel can be used for designing an intelligent PTT system with built-in precise control of photo-thermal temperature.

Inventors

ZHU CHUNLEI
FU HAO

Assignees

南开大学

Dates

Publication Date: 20260508
Application Date: 20230116

Claims (4)

1. The constant temperature photo-thermal system is characterized by comprising the following steps: 1) Obtaining near infrared thermal molecules through one-step Knoevenagel condensation, and preparing near infrared thermal nanoparticles by using amphiphilic polymers through a nano precipitation method; 2) Adding two monomers of N-isopropyl acrylamide and acrylamide by a free radical polymerization method, adding initiator potassium persulfate and cross-linking agent N, N-methylene bisacrylamide, fully mixing uniformly, and polymerizing at room temperature to obtain poly (N-isopropyl acrylamide-acrylamide) hydrogel; 3) Dropping near infrared thermal nano particles on an infected wound, applying poly (N-isopropyl acrylamide-acrylamide) hydrogel on the infected wound, and realizing constant-temperature wound healing under the irradiation of near infrared laser; The near infrared photothermal molecule has a structure shown by a compound 5- (4- (4-methoxyphenyl) diphenylamino) thiophene-2- (1, 3-bis (dicyanomethylene) indane) (MeO-TSI); ; the preparation method of the hydrogel comprises the following steps: 1) Dissolving N-isopropyl acrylamide and acrylamide in a mass ratio of 10:1-50:1 in water, wherein 5mL-10mL of water is needed for every 450 mg of N-isopropyl acrylamide, then adding tetramethyl ethylenediamine serving as an accelerator with the mass of 0.5% -1% of that of N-isopropyl acrylamide, and then adding a cross-linking agent N, N-methylene bisacrylamide with the mass of 1% -2% of that of N-isopropyl acrylamide, and stirring to fully dissolve the N-isopropyl acrylamide and the acrylamide; 2) Adding potassium persulfate with the mass of 0.1-1% of that of the N-isopropyl acrylamide into the fully dissolved aqueous solution, stirring to fully dissolve the N-isopropyl acrylamide, pouring the mixture into a mould, and polymerizing the mixture at room temperature to obtain the thermosensitive poly (N-isopropyl acrylamide-acrylamide) hydrogel.
2. The constant temperature photo-thermal system as claimed in claim 1, wherein the preparation method of the near infrared photo-thermal molecule comprises the following steps: 1) Weighing four compounds 4-bromo-4-methoxytriphenylamine, 5-aldehyde-2-thiopheneboronic acid, potassium carbonate and tetrakis (triphenylphosphine) palladium with the molar ratio of 1:1.5:8:0.05-1:2:10:0.1, vacuumizing and introducing argon for 3-4 times, adding a mixed solution of tetrahydrofuran and water with the volume ratio of 4:1-6:1, heating and reacting for 8-12 hours at 70-75 ℃, and purifying by thin layer chromatography after the reaction is finished to obtain a compound 5- (4- (4-methoxyphenyl) diphenylamino) thiophene-2-formaldehyde; 2) The compound 5- (4- (4-methoxyphenyl) diphenylamino) thiophene-2-formaldehyde and 1, 3-bis (dicyanomethylene) indane with the molar ratio of 1:1.5-1:2 are dissolved in acetic anhydride, wherein 50mL-60mL of acetic anhydride is needed for each gram of 5- (4- (4-methoxyphenyl) diphenylamino) thiophene-2-formaldehyde, the reaction is heated at 60-65 ℃ for 2-6 hours, and after the reaction is finished, the compound 5- (4- (4-methoxyphenyl) diphenylamino) thiophene-2- (1, 3-bis (dicyanomethylene) indane is obtained through thin layer chromatography purification.
3. The constant temperature photo-thermal system as claimed in claim 1, wherein the preparation method of the near infrared photo-thermal nano particles comprises the following steps: 1) Dissolving a compound 5- (4- (4-methoxyphenyl) diphenylamino) thiophene-2- (1, 3-bis (dicyanomethylene) indane) in tetrahydrofuran to prepare mother solution of 1mg/mL-2mg/mL, dropwise adding the prepared mother solution into an amphiphilic polymer poloxamer 188 (F127) aqueous solution of 10mg/mL-15mg/mL under the condition of stirring and argon introducing, dropwise adding 200-250 microliter of mother solution into per milliliter of water, keeping stirring and introducing argon for 20-30 minutes until the tetrahydrofuran is completely removed; 2) Dialyzing the obtained nanoparticle dispersion in ultrapure water for 1-2 days, and freeze-drying to obtain the near infrared thermal nanoparticles.
4. The application of the constant temperature photothermal system in the preparation of an infected wound healing product, which is characterized in that near infrared photothermal nano particles are dripped on the infected wound, the prepared thermosensitive poly (N-isopropyl acrylamide-acrylamide) hydrogel is uniformly coated on the infected wound, and the near infrared photothermal nano particles continuously generate heat under the irradiation of 808nm near infrared laser, so that the thermosensitive poly (N-isopropyl acrylamide-acrylamide) hydrogel is heated to generate phase change and turn white, incident light is effectively scattered, and the near infrared photothermal nano particles cannot continuously generate heat, thereby realizing constant temperature wound healing.

Description

Constant-temperature photo-thermal system and application thereof Technical Field The invention belongs to the biomedical field, relates to a construction method of a constant-temperature photo-thermal system, and particularly relates to application of the constant-temperature system in healing of infected wounds. Background Bacterial infection is one of the major threats to human health, placing a great burden on individuals, society and economy. While the discovery of antibiotics provides a powerful weapon against bacteria for humans, abuse and overuse of antibiotics has led to rapid evolution of drug resistant bacteria. If no emergency measures are taken, the antibiotic resistance crisis may eventually evolve into a global pandemic or multidrug-resistant bacterial epidemic. Therefore, it is of great importance to develop an effective antibiotic therapy that is antibiotic-free. To address this challenge, a great deal of effort has been made to provide various strategies for dealing with antibacterial infections and antibiotic resistance, including surgery, the use of nanomaterials with inherent antibacterial activity, photodynamic therapy and photothermal therapy (PTT), and the like. PTT has become an attractive technique for treating bacterial infections in recent years due to its unique advantages, such as non-invasive, high selectivity and low probability of inducing drug resistance. PTT mainly uses a large amount of heat generated by photo-thermal materials under Near Infrared (NIR) light to destroy bacterial membranes and/or denature bacterial proteins, resulting in swelling and deformation of bacterial cells, which physically destroy the integrity of bacterial cells to inactivate bacteria. And during the course of treatment, bacteria have difficulty developing resistance to PTT by blocking or reducing absorption, increasing metabolism and drug excretion. Despite the tremendous achievement over the past decades, conventional PTT lacks an inherent self-regulating mechanism for precisely controlling temperature, which inevitably causes thermal damage to healthy tissues and/or organs. Due to the great drawbacks of conventional PTT, in order to alleviate the adverse effects of uncontrolled heating, mild PTT at a temperature of less than 50 ℃ is increasingly used by adjusting various experimental parameters such as concentration of photo-thermal material, laser power density, irradiation time, etc. However, such a procedure is cumbersome and has poor reproducibility of the photothermal temperature, and moreover, neglecting the adjustment of the external experimental parameters causes instantaneous overheating and irreversible thermal damage. Therefore, it is very desirable to design a universal constant temperature photothermal system, which can automatically close the photothermal conversion process when the temperature reaches a preset value, so as to safely and effectively solve the problem of bacterial infection. Disclosure of Invention According to the defects of the prior art, the invention discloses a constant-temperature photo-thermal system and application thereof, and the specific technical scheme is as follows: the invention relates to a constant-temperature photo-thermal system, which is constructed by the following steps: 1) Obtaining near infrared thermal molecules through one-step Knoevenagel condensation, and preparing near infrared thermal nanoparticles by using amphiphilic polymers through a nano precipitation method; 2) Adding two monomers of N-isopropyl acrylamide (NIPAM) and Acrylamide (AM) by a free radical polymerization method, adding an initiator potassium persulfate (KPS) and a cross-linking agent N, N-Methylene Bisacrylamide (MBA), fully mixing uniformly, and polymerizing at room temperature to obtain poly (N-isopropyl acrylamide-acrylamide) (P (NIPAM-AM)) hydrogel; 3) The near infrared thermal nano particles are dripped on an infected wound, then P (NIPAM-AM) hydrogel is applied to the infected wound, and constant-temperature wound healing is realized under the irradiation of near infrared laser. In the constant temperature photo-thermal system, a near infrared photo-thermal molecule has a structure shown by a compound 5- (4- (4-methoxyphenyl) diphenylamino) thiophene-2- (1, 3-bis (dicyanomethylene) indane) (MeO-TSI); the preparation method of the near infrared photo-thermal molecule comprises the following steps: 1) Weighing four compounds 4-bromo-4-methoxytriphenylamine, 5-aldehyde-2-thiopheneboronic acid, potassium carbonate and tetrakis (triphenylphosphine) palladium with the molar ratio of 1:1.5:8:0.05-1:2:10:0.1, vacuumizing and introducing argon for 3-4 times, and adding a mixed solution of tetrahydrofuran and water with the volume ratio of 4:1-6:1. Heating and reacting for 8-12 hours at 70-75 ℃, and purifying by thin layer chromatography after the reaction is finished to obtain a compound 5- (4- (4-methoxyphenyl) diphenylamino) thiophene-2-formaldehyde; 2) The compound