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Multi-functional stealth nanoparticle co-loaded with VP and AQ4N and modified by cRGDfK polypeptide and application thereof

A peptide modification and nanoparticle technology, applied in the field of medicine, can solve problems such as impairing the prognosis of patients, and achieve the effects of strong in vitro targeting, enhanced anti-tumor effect, and enhanced curative effect.

Active Publication Date: 2018-12-28
SHANGHAI JIAOTONG UNIV SCHOOL OF MEDICINE
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

[0004] Utilizing the hypoxic state of tumor tissue induced by tumor blood vessel targeting photodynamic therapy, the hypoxia-activated prodrug can be co-delivered, and the hypoxic environment can be used to further kill residual tumor cells and achieve the effect of enhancing the curative effect; on the other hand, tumor hypoxia Inducible factor HIF-1α is an important product in the hypoxic environment of tumor tissue, which plays an important role in related downstream signaling pathways in tumor tissue, and seriously damages the prognosis of patients after photodynamic therapy.

Method used

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  • Multi-functional stealth nanoparticle co-loaded with VP and AQ4N and modified by cRGDfK polypeptide and application thereof
  • Multi-functional stealth nanoparticle co-loaded with VP and AQ4N and modified by cRGDfK polypeptide and application thereof
  • Multi-functional stealth nanoparticle co-loaded with VP and AQ4N and modified by cRGDfK polypeptide and application thereof

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1c

[0036] Example 1 Construction of cRGDfK-pGO-VP-AQ4N and its therapeutic effect

[0037] (1) cRGDfK-pGO-VP-AQ4N dual-mode nano drug delivery system

[0038] Graphene oxide (GO) was synthesized according to the improved Hummers method. 0.05M NaOH was added to the GO suspension, and the water bath was sonicated for 5h to convert the ester groups, hydroxyl groups, epoxides and other groups existing on GO into carboxyl groups (-COOH) , concentrated hydrochloric acid to adjust the pH of the GO solution to 1, and wash the GO solution with double distilled water to neutrality. Catalyzed by EDC (5mM) and NHS (5mM), pGO was obtained by reacting the amino terminal of 8-arm PEG with the carboxyl group of GO. Add VP and AQ4N to the pGO solution in turn and stir overnight. The dosage of VP, AQ4N and pGO is 0.75mg / ml, 1mg / ml, 5mg / ml in turn, and the VP and AQ4N with aromatic ring molecular structure will be separated by π-π stacking effect Sequentially loaded on the surface of pGO to obtai...

Embodiment 2c

[0056] Example 2 Construction of cRGDfK-pGO-VP-AQ4N and its therapeutic effect

[0057] Graphene oxide (GO) was synthesized according to the improved Hummers method. 0.05M NaOH was added to the GO suspension, and the water bath was sonicated for 5h to convert the ester groups, hydroxyl groups, epoxides and other groups existing on GO into carboxyl groups (-COOH) , concentrated hydrochloric acid to adjust the pH of the GO solution to 1, and wash the GO solution with double distilled water to neutrality. Catalyzed by EDC (5mM) and NHS (5mM), pGO was obtained by reacting the amino terminal of 8-arm PEG with the carboxyl group of GO. Add VP and AQ4N to the pGO solution in turn and stir overnight. The dosages of VP, AQ4N and pGO are 0.5mg / ml, 1.5mg / ml, and 8mg / ml in sequence. AQ4N was sequentially loaded on the surface of pGO to obtain pGO-VP-AQ4N. Using BS3 catalysis, cRGDfK polypeptide was modified on the surface of nanoparticles to obtain cRGDfK-pGO-VP-AQ4N. The dosage of cata...

Embodiment 3c

[0059] Example 3 Construction of cRGDfK-pGO-VP-AQ4N and its therapeutic effect

[0060] Graphene oxide (GO) was synthesized according to the improved Hummers method. 0.05M NaOH was added to the GO suspension, and the water bath was sonicated for 5h to convert the ester groups, hydroxyl groups, epoxides and other groups existing on GO into carboxyl groups (-COOH) , concentrated hydrochloric acid to adjust the pH of the GO solution to 1, and wash the GO solution with double distilled water to neutrality. Catalyzed by EDC (5mM) and NHS (5mM), pGO was obtained by reacting the amino terminal of 8-arm PEG with the carboxyl group of GO. Add VP and AQ4N to the pGO solution in turn and stir overnight. The dosages of VP, AQ4N and pGO are 1.5 mg / ml, 0.8 mg / ml, and 7 mg / ml in turn. The VP with aromatic ring molecular structure and AQ4N was sequentially loaded on the surface of pGO to obtain pGO-VP-AQ4N. Using BS3 catalysis, the cRGDfK polypeptide is modified on the surface of nanopartic...

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PUM

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Abstract

The invention relates to a multi-functional stealth nanoparticle co-loaded with VP and AQ4N and modified by cRGDfK polypeptide and application thereof. The stealth nanoparticle is composed of oxidizedgraphene, cRGDfK polypeptide, photosensitizer verteporfin and anoxic activated prodrug AQ4N. According to the multi-functional stealth nanoparticle co-loaded with the VP and the AQ4N and modified bythe cRGDfK polypeptide and the application thereof, the anoxic state of tumor tissue induced by tumor vascular targeted photodynamic therapy is utilized to delivery the anoxic activated prodrug together, and the anaerobic environment is utilized to further kill residual tumor cells. The multi-functional stealth nanoparticle co-loaded with the VP and the AQ4N and modified by the cRGDfK polypeptideand the application thereof have the advantages that the drug loading capacity of a cRGDfK-pGO-VP-AQ4N nanoparticle is high, the targeting ability is strong, and the killing and anti-tumor effects ontumor cells are significantly enhanced.

Description

technical field [0001] The invention relates to the technical field of medicine, in particular to a cRGDfK polypeptide-modified multifunctional stealth nanoparticle co-carrying VP and AQ4N and its preparation method and application. Background technique [0002] As a light-triggered tumor treatment method that has been transformed into clinical applications, photodynamic therapy has attracted much attention due to its minimally invasive, unique selectivity and safety. The main principle is to efficiently introduce photosensitizers into tumor cells, and irradiate the lesion area with a light source of a specific wavelength, so that the photosensitizers absorbed by the tissue are stimulated, and reactive oxygen species are generated to cause tumor cell death, microvascular damage, and induce local immune reactions. According to reports, photodynamic therapy can be cured in the early stage of tumors. For patients who have lost the chance of surgery, photodynamic therapy can als...

Claims

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Application Information

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IPC IPC(8): A61K47/69A61K47/64A61K47/52A61K41/00A61P35/00A61K31/136
CPCA61K31/136A61K41/0071A61K2300/00
Inventor 方超栾鑫管滢芸陆琴赵梅陈红专
Owner SHANGHAI JIAOTONG UNIV SCHOOL OF MEDICINE
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