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Slightly acidic environment targeted polypeptide modified tumor targeted nano drug delivery system, and preparation method thereof

A technology for targeting peptides and a slightly acidic environment, applied in the biological field, can solve problems such as low targeting efficiency, and achieve the effects of improving efficiency, simple preparation method, and high tumor targeting efficiency.

Inactive Publication Date: 2014-04-09
FUDAN UNIV
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

[0007] The purpose of the present invention is to provide a novel tumor-targeted nano drug delivery system modified by targeting polypeptides in a slightly acidic environment, so as to better solve the problem of low targeting efficiency existing in the existing tumor-targeted drug delivery system

Method used

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  • Slightly acidic environment targeted polypeptide modified tumor targeted nano drug delivery system, and preparation method thereof
  • Slightly acidic environment targeted polypeptide modified tumor targeted nano drug delivery system, and preparation method thereof
  • Slightly acidic environment targeted polypeptide modified tumor targeted nano drug delivery system, and preparation method thereof

Examples

Experimental program
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Effect test

Embodiment 1

[0054] Dissolve polylysine in an appropriate amount of methanol to prepare a 10mg / ml solution, take 100μl and dry it in a vial; dissolve polyethylene glycol maleimide-polyethylene glycol 3500-succinimide in An appropriate amount of 0.035MpH 8.0 phosphate buffer solution was prepared into a 5 mg / ml working solution, and 318 μl of polyethylene glycol working solution was added to a vial, and stirred and reacted at room temperature for 2 hours to obtain polylysine-polyethylene glycol ( DGL-PEG 10 ); the N-terminus of pHLIP is connected with a cysteine ​​to form pHLIP with free sulfhydryl groups. Then dissolve the pHLIP peptide in an appropriate amount of dimethyl sulfoxide to prepare a 1 mg / ml peptide solution, take 182 μl and add it to the polylysine-polyethylene glycol solution, then add 500 μl pH 7.0 phosphate buffer solution, and Stirring reaction at room temperature for 24h, the prepared polylysine-polyethylene glycol-polypeptide (DGL-PEG 10 -pHLIP 1 ) into a MWCO 5000 ul...

Embodiment 2

[0056] Dissolve polylysine in an appropriate amount of methanol to prepare a 10mg / ml solution, take 100μl and dry it in a vial; dissolve polyethylene glycol maleimide-polyethylene glycol 3500-succinimide in An appropriate amount of 0.035MpH 8.0 phosphate buffer solution was prepared into a 5 mg / ml working solution, and 318 μl of polyethylene glycol working solution was added to a vial, and stirred and reacted at room temperature for 2 hours to obtain polylysine-polyethylene glycol ( DGL-PEG 10 ); the N-terminus of pHLIP is connected with a cysteine ​​to form pHLIP with free sulfhydryl groups. Then dissolve the pHLIP peptide in an appropriate amount of dimethyl sulfoxide to prepare a 1 mg / ml peptide solution, take 182 μl and add it to the polylysine-polyethylene glycol solution, then add 500 μl pH 7.0 phosphate buffer solution, and Stirring reaction at room temperature for 24h, the prepared polylysine-polyethylene glycol-polypeptide (DGL-PEG 10 -pHLIP 1 ) into a MWCO 5000 ul...

Embodiment 3

[0058] Dissolve polylysine in an appropriate amount of methanol to prepare a 10mg / ml solution, take 100μl and dry it in a vial; dissolve polyethylene glycol maleimide-polyethylene glycol 3500-succinimide in An appropriate amount of 0.035MpH 8.0 phosphate buffer solution was prepared into a 5 mg / ml working solution, and 318 μl of polyethylene glycol working solution was added to a vial, and stirred and reacted at room temperature for 2 hours to obtain polylysine-polyethylene glycol ( DGL-PEG 10 ), half of it was transferred to a MWCO 5000 ultrafiltration centrifuge tube, and the unreacted polyethylene glycol 3500 was removed by ultrafiltration at 12000rpm for 30 minutes to obtain an unmodified carrier, which was redissolved in ultrapure water into a centrifuge tube; the N-terminus of pHLIP was connected to a cysteine, forming pHLIP with a free sulfhydryl group. The other half continues to react, dissolve the pHLIP peptide in an appropriate amount of dimethyl sulfoxide, prepare...

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Abstract

The invention belongs to the field of biotechnology, and relates to a slightly acidic environment targeted polypeptide modified tumor targeted nano drug delivery system, and a preparation method thereof. The slightly acidic environment targeted polypeptide modified tumor targeted nano drug delivery system is prepared via self-assembly of a slightly acidic environment targeted polypeptide modified dendrimer encapsulated gene, wherein the surface of the dendrimer is rich of amino groups. According to the preparation method, a polypeptide of transmembrane helix protein C derived from bacteria visual purple is used for modifying a high molecular carrier, enrichment and adhesion onto cells is realized via a pH sensitive cell membrane insertion method, and entering into cells is realized via electrostatic adsorption guided endocytosis, so that untaking of tumor cells on drugs is improved, and toxic and side effects are reduced. According to the tumor targeted nano drug delivery system, cell membrane is taken as the target point, and the polypeptide is taken as the target head group in tumor slightly acidic environment, targeting and curing efficiency are high, the preparation method is simple and convenient, and tumor cell drugs, which are derived from human or animal, and is used for targeted therapy, can be prepared.

Description

technical field [0001] The invention belongs to the field of biological technology and relates to a drug delivery system, in particular to a tumor-targeting nano drug delivery system modified by a slightly acidic environment targeting polypeptide and a preparation method thereof. Background technique [0002] In recent years, research on anticancer drug delivery has attracted much attention. The anticancer drugs are different from common drugs, which have high toxic and side effects and cause great damage to the normal organs of the body; it is imperative to effectively and exclusively transport the anticancer drugs to the tumor site to reduce the toxic and side effects and the resulting economic losses. [0003] Studies have pointed out that the tumor-targeted drug delivery system is a new drug delivery strategy for the treatment of tumors. There are mainly two strategies for the construction of the targeted drug delivery system: passive targeting and active targeting; pas...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): A61K9/14A61K48/00A61K47/42A61K47/34A61P35/00
Inventor 韩亮蒋晨
Owner FUDAN UNIV
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