Biological cascade reaction type photodynamic integrated biopolymer, preparation method and applications thereof

A technology of biopolymers and cascade reactions, applied in drug combinations, medical preparations containing active ingredients, pharmaceutical formulations, etc., can solve problems such as transmission and driving obstacles, achieve enhanced retention, increase tumor retention rate, and enhance blood loop effect

Active Publication Date: 2020-04-21
CHONGQING UNIV
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

However, its clinical translation is hampered by a series of issues related to the delivery and actuation of light-activated photosensitizers (PS), which are usually highly hydrophobic and tend to aggregate in aqueous environments, leading to rapid clearance and self-quenching; An optimal PDT nanoformulation strategy should be highly tumor-specific during systemic redistribution while being able to deliver PS molecules in a single-molecule manner after tumor uptake.

Method used

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  • Biological cascade reaction type photodynamic integrated biopolymer, preparation method and applications thereof
  • Biological cascade reaction type photodynamic integrated biopolymer, preparation method and applications thereof
  • Biological cascade reaction type photodynamic integrated biopolymer, preparation method and applications thereof

Examples

Experimental program
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Effect test

Embodiment 1

[0044] Preparation of a biological cascade reaction photodynamic integrated biopolymer (PEG 4000 -CDM-ZnPc-S-S-HA), proceed as follows:

[0045] 1. Preparation of tetraamino zinc phthalocyanine (ZnPc):

[0046] (1) Put 4.1g 4-nitrophthalimide, 10g urea and 0.05g ammonium molybdate in a three-necked flask, heat to melt, add 1.2g zinc chloride hexahydrate and heat to 160℃, continue React until no bubbles are generated in the flask. After cooling, wash with 1mol / L HCL and 1mol / L NaOH solution, then wash with ultrapure water to neutrality, and vacuum dry to obtain a blue-purple product;

[0047] (2) Add the blue-violet product and 2.88g sodium sulfide nonahydrate into a three-necked flask, heat and add 15ml DMF to fully dissolve it. After heating to 60°C, increase the stirring speed. After reacting for 1h, wash with water until neutral, vacuum After drying and removing the solvent, a dark green solid substance, namely the product to be prepared, tetraamino zinc phthalocyanine (ZnPc), is...

Embodiment 2

[0065] The biological cascade reaction type photodynamic integrated biopolymer (PEG) prepared in Example 1 4000 -CDM-ZnPc-S-S-HA) for in vitro simulation experiments under acidic conditions:

[0066] The biological cascade reaction type photodynamic integrated biopolymer (PEG) prepared in Example 1 4000 -CDM-ZnPc-S-S-HA) TEM image such as figure 1 As shown in a, it can be seen that the polymer (PEG 4000 -CDM-ZnPc-S-S-HA) is an irregular macromolecule and does not form nanoparticles. Next, the biological cascade reaction type photodynamic integrated biopolymer (PEG) prepared in Example 1 4000 -CDM-ZnPc-S-S-HA) is treated under acidic conditions of pH=6.5, the TEM and SEM images of the treated product are as follows figure 1 As shown in b and c, it can be seen that the polymer has formed nanoparticles after being treated in acidic conditions of pH=6.5, indicating that the biological cascade reaction type photodynamic integrated biopolymer (PEG 4000 -CDM-ZnPc-S-S-HA) can self-assemble...

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Abstract

The invention relates to a biological cascade reaction type photodynamic integrated biopolymer, a preparation method and applications thereof, and belongs to the field of medicine preparation. According to the biological cascade reaction type photodynamic integrated biopolymer (PEG4000-CDM-ZnPc-S-S-HA), a photosensitizer zinc phthalocyanine (ZnPc) and PEG 4000 are combined through a pH-acid responsive maleic acid amide linker; and the combined material is immobilized on a hyaluronic acid (HA) chain by using a disulfide linker capable of being cracked by oxidation reduction, wherein the PEG segment can enhance the blood circulation of a molecular carrier after intravenous administration to fall off after reaching an acidic tumor microenvironment, so that the residual ZnPc-S-S-HA is self-assembled into a large cluster in situ so as to avoid reverse diffusion and improve the tumor retention rate, and due to hydrophilicity, degradability and the capacity of specifically combining with CD44overexpressed on a tumor cell membrane, HA is used as a carrier substrate and a tumor targeting ligand.

Description

Technical field [0001] The invention belongs to the field of medicine preparation, and specifically relates to a biological cascade reaction type photodynamic integrated biopolymer and a preparation method and application thereof. Background technique [0002] The size of nanomaterials is a key factor in determining the mode of interaction between nanomaterials and the biological environment, and may fundamentally affect their functional performance in clinical applications. From a clinical point of view, large-size nanoparticles (20-200nm) usually show better tumor aggregation effects due to the enhanced penetration and retention (EPR) effect, while small-size nanoparticles ( <10nm) Due to better diffusion fluidity, it often has a strong tumor penetration ability. The emergence of supramolecular nanotechnology provides new opportunities to combine the advantages of large and small nano-biological materials, the most common of which is to use the self-assembly of nanoparticles...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): C08G81/00C08G65/337C08G65/334C08G65/333A61K41/00A61P35/00
CPCA61K41/0071A61P35/00C08G65/33306C08G65/33331C08G65/3348C08G65/337C08G81/00
Inventor 罗忠王璇侯彦华李孟桓胡燕
Owner CHONGQING UNIV
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