A method and application for increasing the level of ROS by promoting the conversion of energy absorbed by photosensitizers into the CET pathway

A photosensitizer and pathway technology, applied in the field of photodynamic therapy, can solve the problems of lack of tumor-specific targeting of photosensitizers, limit the clinical application of PDT, and low ROS, so as to enhance the effect of PDT, inhibit the photothermal transition pathway, and increase the content of Effect

Active Publication Date: 2022-03-08
SICHUAN UNIV
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

At the same time, due to the lack of tumor-specific targeting of most photosensitizers, the photosensitizers accumulate less in the tumor site and generate lower ROS, which limits the clinical application of PDT.

Method used

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  • A method and application for increasing the level of ROS by promoting the conversion of energy absorbed by photosensitizers into the CET pathway
  • A method and application for increasing the level of ROS by promoting the conversion of energy absorbed by photosensitizers into the CET pathway
  • A method and application for increasing the level of ROS by promoting the conversion of energy absorbed by photosensitizers into the CET pathway

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0038] A method for increasing the level of ROS by promoting the energy absorbed by the photosensitizer into the CET pathway, comprising the following steps:

[0039] (1) Accurately weigh 20 mg of IR780 and dissolve in 2 mL of methanol to obtain IR780 stock solution (10 mg / mL);

[0040] (2) Take 200 μL of IR780 storage solution, and then add 10 μL of BF to it; use ultrasound to mix the two thoroughly, drop them into 5 mL of water, and stir at 40°C for 5 minutes to obtain carrier-free nano-drug (RF) aqueous solution;

[0041] (3) Add 300 μL hyaluronic acid aqueous solution (2 mg / mL) to the RF aqueous solution, and vortex fully to obtain the HA-coated carrier-free nanomedicine (HRF) aqueous solution.

Embodiment 2

[0042] Example 2 Carrier-free nano drug stability and enzyme sensitivity test

[0043] Disperse HRF in phosphate buffered saline (PBS, pH=7.4) and a solution containing 10% fetal bovine serum (FBS), and use DLS to measure the particle size and potential and observe its change. Such as figure 1 As shown, the particle size and potential of HRF did not change greatly in PBS and 10% FBS, which indicated that HRF was relatively stable in the physiological environment.

[0044] Incubate HRF with hyaluronidase (100-250units / mL) at pH = 5.5, 37°C for 4 hours, and use DLS to measure the particle size of the carrier-free nano-drug at 0.5, 1, 2, and 4 hours. The results are shown in figure 2 . Such as figure 2 As shown, after incubation with hyaluronidase, the diameter of HRF increased significantly, and the polydispersity index (PdI) increased from 0.1 to 0.7. This phenomenon can be attributed to the degradation of the HA shell of the nanocarrier by hyaluronidase, which disrupts ...

Embodiment 3

[0045] Example 3 Using computer simulation to verify the self-assembly of fluorocarbon molecules to drive the formation of photosensitizers

[0046] 1. Simulate the self-assembly of IR780 and pentafluorophenyl trifluoroacetate (F) at the ratio of 1:1, 1:5, 1:10 and 1:20 respectively. See the results image 3 -A. In the figure, the dark molecule is IR780 and the light molecule is F. When the ratio was 1:1, F spontaneously formed worm-like nanoparticles to drive the assembly of IR780, forming irregular worm-like nanoparticles. As the proportion of F increases, F molecules first aggregate into spherical nanoparticles, and then drive IR780 to disperse and assemble on its surface.

[0047] 2. Then the ratio of IR780 and F was fixed at 1:20, and a regular scan was performed to explore the dynamic process of self-assembly of IR780 driven by fluorocarbons. The results are shown in image 3 -B. At 0 ps, ​​IR780 and F molecules are randomly distributed in water. Over time, F starts...

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Abstract

The invention discloses a method and application for increasing the ROS level by promoting the conversion of the energy absorbed by the photosensitizer into the CET pathway. The method comprises the following steps: uniformly ultrasonically mix the dissolved photosensitizer and small molecular fluorocarbon compound, then dropwise add it to water, and stir at 40-60°C for 5-10 minutes; the small molecular fluorocarbon compound can drive the photosensitizer to automatically Assembled to form nanoparticles, this self-assembly strategy can reduce the aggregation of photosensitizer molecules, thereby improving the conversion of the energy absorbed by the photosensitizer to the CET pathway, increasing the level of ROS produced by it, thereby enhancing the efficacy of PDT. The invention can effectively solve the problem of insufficient enhancement of CET by encapsulating the photosensitizer by nano-encapsulation technology at present, and increase the content of ROS generated by the photosensitizer.

Description

technical field [0001] The invention belongs to the technical field of photodynamic therapy, and specifically relates to a method and application for increasing ROS level by promoting the conversion of energy absorbed by a photosensitizer into a CET pathway. Background technique [0002] Photodynamic therapy (PDT) represented by reactive oxygen species (ROS) has attracted increasing attention, and since ROS levels are positively correlated with antitumor outcomes, the pursuit of generating more ROS is crucial for improving antitumor efficacy. To increase ROS levels, currently common strategies are to improve tumor site hypoxia and reduce GSH-induced ROS consumption. In recent years, strategies to convert absorbed energy into ROS by enhancing photosensitizers have attracted great attention of researchers. [0003] At present, the commonly used strategies of nanocarriers by loading or encapsulating photosensitizers will inevitably lead to aggregation or random spatial distrib...

Claims

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Application Information

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Patent Type & Authority Patents(China)
IPC IPC(8): A61K41/00A61K47/46A61P35/00B82Y5/00
CPCA61K41/0057A61K47/46A61P35/00B82Y5/00
Inventor 曹俊梅衡雷蕾张学全朱海何斌
Owner SICHUAN UNIV
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