iNGR-modified targeted self-assembly RNAi NANO drug delivery system for brain glioma and preparation method of system

A drug delivery system, brain glioma technology, applied in the field of brain glioma targeted self-assembled RNAi nano drug delivery system and its preparation, to achieve the effects of improved delivery efficiency, good endogenous properties, and ideal clinical application prospects

Active Publication Date: 2016-01-27
FUDAN UNIV
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  • Abstract
  • Description
  • Claims
  • Application Information

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Problems solved by technology

However, for an effective tumor-targeted drug delivery system, it is far from enough to only have the surface targeting properties of new blood vessels. The key is to achieve efficient blood vessel leakage, penetrate tumor tissue, and reach tumor cells

Method used

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  • iNGR-modified targeted self-assembly RNAi NANO drug delivery system for brain glioma and preparation method of system
  • iNGR-modified targeted self-assembly RNAi NANO drug delivery system for brain glioma and preparation method of system
  • iNGR-modified targeted self-assembly RNAi NANO drug delivery system for brain glioma and preparation method of system

Examples

Experimental program
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Effect test

Embodiment 1

[0036] OEI and DTSSP were dissolved in pure water at a molecular ratio of 1:1, shaken at 35°C for 48 hours to generate pOEI, and unreacted monomers were removed by ultrafiltration. pOEI and PEG containing bifunctional groups were dissolved in PBS at pH 8.0 at a molecular ratio of 1:10, stirred at room temperature for 2 hours, and unreacted substances were removed by ultrafiltration to obtain pOEI-PEG-SH; iNGR cyclic peptide and Sulfo- LC-SMPT was dissolved in PBS at pH 7.2 at a molecular ratio of 1:1, stirred at room temperature for 2 hours, and unreacted substances were removed by ultrafiltration to obtain Sulfo-LC-iNGR. pOEI-PEG-SH and Sulfo-LC-iNGR were mixed according to the molecular ratio of 1:5, reacted at room temperature for 2 hours, and the unreacted substances were removed by ultrafiltration to obtain pOEI-PEG-LC-iNGR, whose hydrogen spectrum was as follows figure 1 (a) shown.

Embodiment 2

[0038] Two primer molecules containing specific sequences and T 4 The ligase was added to the same reaction system, heated at 95°C for 2 minutes, and gradually cooled to room temperature within 1 hour to obtain the transcription template molecule. Appropriate amount of template molecules, AUCG four nucleotides, in vitro RNA transcriptase, etc. were added to the same reaction system, 37°C constant temperature for 28h transcription, DNase was added at 37°C constant temperature for 10min to terminate the transcription reaction, and self-assembled RNAi nanoparticles were obtained.

Embodiment 3

[0040] The pOEI-PEG-LC-iNGR prepared in Example 1 was combined with the spongy and loose RNAi nanoparticles prepared in Example 2 at a mass ratio of 10:1 for 30 seconds to obtain compressed pOEI-PEG-LC-iNGR / RNAi Nanoparticles; gel electrophoresis results show that they can form complete encapsulation when the mass ratio is 10:1, and have specific sensitivity to the high concentration of glutathione in tumor cells (such as figure 1 (c) shown).

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Abstract

The invention belongs to the field of biotechnology and relates to an iNGR-modified targeted self-assembly RNAi nano drug delivery system for brain glioma and preparation of the system. A synthetic glutathione-sensitive cationic polymer is utilized to compress spongy loose RNAi nanospheres, and a hydrophilic polymer is utilized for modification to build the ideal-grain-size and reduction-sensitive RNAi nano drug delivery system. The iNGR-modified targeted self-assembly RNAi nano drug delivery system is not only a carrier but also a medicine per se, the in-vivo siRNA delivery efficiency can be remarkably improved, the in-vivo immune reaction and toxic or/and side effects are effectively reduced, and the security of the RNAi nano delivery system is guaranteed. Targeted head-group iNGR tumor penetrating cyclopeptide in the system has favorable tumor angiogenesis targeting effect and tumor tissue penetration capability, and can effectively increase accumulation of the RNAi nano drug delivery system in tumor cells to achieve an excellent brain glioma treatment effect.

Description

technical field [0001] The invention belongs to the field of biological technology, and relates to a novel gene drug delivery system and a preparation method thereof, in particular to an iNGR-modified brain glioma targeting self-assembly RNAi nano drug delivery system and a preparation method thereof. Background technique [0002] Prior art reports that glioma is one of the most devastating human diseases. Traditional treatment methods (such as: surgical resection, radiotherapy, chemotherapy, etc.) generally have unavoidable side effects, poor effect and high recurrence rate. Studies have shown that RNA interference (RNAi) therapy can significantly reduce the expression of specific functional proteins in tumor cells, thereby inhibiting the occurrence and development of the disease, and is accompanied by very few side effects. It has been widely accepted as the safest and most effective treatment for glioma. Methods. Common RNAi therapy is achieved by encapsulating small in...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): A61K48/00A61K47/44A61K47/34A61P35/00
Inventor 蒋晨安赛
Owner FUDAN UNIV
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