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Tumor cell membrane/nuclear membrane double-targeting tumor nano-drug slow-release system and preparation and application thereof

A nano-drug and tumor drug technology, applied in the field of biomedicine, can solve the problems of unsatisfactory treatment effect of liver cancer, and achieve the effects of inhibiting tumor growth, low synthesis cost and simple method.

Inactive Publication Date: 2015-10-21
GUANGXI MEDICAL UNIVERSITY
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

[0008] Although some progress has been made in the treatment of liver cancer in recent years, the treatment effect of liver cancer is still unsatisfactory.

Method used

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  • Tumor cell membrane/nuclear membrane double-targeting tumor nano-drug slow-release system and preparation and application thereof
  • Tumor cell membrane/nuclear membrane double-targeting tumor nano-drug slow-release system and preparation and application thereof
  • Tumor cell membrane/nuclear membrane double-targeting tumor nano-drug slow-release system and preparation and application thereof

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0074] Example 1. Preparation of Tumor Cell Membrane / Nuclear Membrane Dual Targeting Tumor Nano-Drug Sustained Release System

[0075] The nano-drug slow-release system provided by the present invention is a tumor cell membrane / nuclear membrane double-targeted tumor nano-drug slow-release system, such as figure 1 As shown, its name is TLS11a-LB-TATp-MSN / DOX.

[0076] TLS11a-LB-TATp-MSN / DOX, is a nanoparticle composed of core (TATp-MSN / DOX) and shell (TLS11a-LB), the shell is composed of aptamer (TLS11a), PEG and nanoliposome, TLS11a Linked by PEG and nanoliposomes, TLS11a can specifically recognize liver cancer cells, and the nucleotide sequence of the aptamer TLS11a is SEQ ID No.2 in the sequence listing; TATp-MSN / DOX is a nanomaterial modified by a polypeptide (TATp) ( Mesoporous silica nanomaterial, MSN) and the antitumor drug (DOX) loaded in the nanomaterial modified by the polypeptide, TATp can penetrate the nucleus membrane, and the amino acid sequence of the polypeptid...

Embodiment 2

[0111] The therapeutic effect of TLS11a-LB-TATp-MSN / DOX of embodiment 2 and embodiment 1 on tumor

[0112] Suspend the TLS11a-LB-TATp-MSN / DOX, TATp-MSN / DOX, TLS11a-LB-MSN / DOX, TLS11a-LB-TATp-MSN and LB-TATp-MSN / DOX of Example 1 with PBS, respectively, Obtain TLS11a-LB-TATp-MSN / DOX injection, TATp-MSN / DOX injection, TLS11a-LB-MSN / DOX injection, TLS11a-LB-TATp-MSN injection with adriamycin content of 6 μg / μL and LB-TATp-MSN / DOX injection. DOX was dissolved in PBS to obtain DOX injection with a doxorubicin content of 6 μg / μL.

[0113] 6-8 weeks old inbred female nude mice (BALB / c Nude Mice) were subcutaneously inoculated with 2×10 6 H22 tumor cells. Measure the long diameter and short diameter of the tumor twice a week, according to the formula TV=1 / 2×a×b 2 Calculate the tumor volume. When the average volume of the tumor grows to about 10mm 3 Tumor-bearing BalB / c nude mice were obtained. Inject 200 μL of the above TLS11a-LB-TATp-MSN / DOX injection into the tail vein of each...

Embodiment 3

[0125] Example 3, the influence of TLS11a and TATp on the targeting effect of TLS11a-LB-TATp-MSN / DOX

[0126] 1. The effect of TATp on the targeting effect of TLS11a-LB-TATp-MSN / DOX

[0127] A fat-soluble red fluorescent dye Di I is marked on the TLS11a-LB obtained in Step S6 of Example 1 to obtain TLS11a-LB (DiI-TLS11a-LB) labeled with the red fluorescent dye DiI, which is obtained in Step S1 of Example 1 Green fluorescent FITC is marked on the MSN and the TATp-MSN obtained in step S2 to obtain green fluorescent FITC-labeled MSN (FITC-MSN) and green fluorescent FITC-labeled TATp-MSN (FITC-TATp-MSN).

[0128] According to the preparation method of TLS11a-LB-TATp-MSN / DOX in Example 1, the TATp-MSN / DOX obtained in step S4 was replaced with the above-mentioned FITC-MSN, and the aptamer TLS11a modified lipid double obtained in step S6 was The molecular layer (TLS11a-LB) was replaced with the above-mentioned Di I-TLS11a-LB, and the other steps were kept unchanged to obtain a syste...

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Abstract

The invention discloses a tumor cell membrane / nuclear membrane double-targeting tumor nano-drug slow-release system and preparation and application thereof. The tumor cell membrane / nuclear membrane double-targeting tumor nano-drug slow-release system is a nano particle composed of a nucleus and a shell, wherein the shell is composed of an aptamer, PEG and nano liposomes, and the aptamer is connected with the nano liposome through the PEG and capable of specifically recognizing a tumor cell; the nucleus is composed of a nano material modified by polypeptide and an antineoplastic drug carried by the nano material modified by the polypeptide, and the polypeptide is capable of penetrating through a cell nucleus nuclear membrane. It is proved through experiments that the tumor cell membrane / nuclear membrane double-targeting tumor nano-drug slow-release system can inhibit tumor growth and prolong the survival time of a tumor-bearing animal and can be used for treating a tumor.

Description

technical field [0001] The invention relates to a tumor cell membrane / nuclear membrane double-targeted tumor nano drug sustained release system in the field of biomedicine and its preparation and application. Background technique [0002] Liver cancer is one of the most common clinical tumors, and its incidence is increasing year by year, seriously threatening human health. Guangxi Zhuang Autonomous Region is a high-incidence area of ​​liver cancer in my country, and its death rate is twice that of the whole country. Liver cancer often has a high degree of malignancy, is difficult to treat, and metastasizes early, and is often found in the middle and late stages, losing the opportunity for surgical treatment. Although new treatment techniques are constantly updated, surgery, chemotherapy, and radiotherapy are still the mainstays of cancer treatment. Chemotherapy drugs can directly kill cancer cells, which is one of the most ideal and most effective treatment methods. [0...

Claims

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Application Information

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IPC IPC(8): A61K9/51A61K47/34A61K47/42A61K45/06A61K31/704A61P35/00
Inventor 卢小玲赵永祥
Owner GUANGXI MEDICAL UNIVERSITY
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