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Preparing method of chondriosome-targeted multilayer tumor deep-penetration sound sensitizer with sound responsiveness

A deep penetrating sound and mitochondrial technology, applied in the field of biomedicine, can solve the problems of uneven distribution, poor penetration ability in deep tumor areas, and low accumulation efficiency of sound sensitizers, so as to ensure the effect of treatment

Inactive Publication Date: 2019-04-19
CHONGQING MEDICAL UNIVERSITY
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

[0004] The purpose of the present invention is to provide a method for preparing a mitochondria-targeted, acoustically responsive, multi-layer tumor deep-penetrating sonosensitizer to solve the problem of the low accumulation efficiency of existing sonosensitizers in tumors and the penetration into deep tumor regions Problems with poor capacity and uneven distribution within the tumor

Method used

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  • Preparing method of chondriosome-targeted multilayer tumor deep-penetration sound sensitizer with sound responsiveness
  • Preparing method of chondriosome-targeted multilayer tumor deep-penetration sound sensitizer with sound responsiveness
  • Preparing method of chondriosome-targeted multilayer tumor deep-penetration sound sensitizer with sound responsiveness

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Experimental program
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Effect test

Embodiment 1

[0031] A method for preparing a mitochondria-targeted, acoustic-responsive, multi-layer tumor deep-penetrating sonosensitizer, specifically comprising the following steps:

[0032] (1) Synthesis of lipid film with IR780: Mix DPPC, DSPE-PEG2000, cholesterol and IR780 (12:4:4:1 by mass ratio), dissolve in 5ml chloroform, transfer to a round bottom flask for rotary evaporation , forming a lipid film;

[0033] (2) Use 4ml of PBS to hydrate the lipid film, add 400μL of PFP, and in the ice bath, under the condition of sonic shock with an intensity of 125W, sonic shock for 5 minutes (5 minutes in the mode of shaking for 5s and pausing for 5s), and finally centrifuge (6000rpm, 5min) to prepare the sound sensitizer IR780-NDs.

Embodiment 2-9 and comparative example 1-2

[0035] The difference between Examples 2-5 and Example 1 lies in the mass ratio of DPPC, DSPE-PEG2000, cholesterol and IR780, and the difference between Examples 6-9 and Example 1 lies in the intensity of the acoustic shock, see Table 1 below for details.

[0036] Comparative example 1 is a blank nano-droplet with unmodified IR780 in the shell (hereinafter referred to as NDs). The difference between the preparation method of comparative example 1 (NDs) and the sound sensitizer IR780-NDs is that IR780 is not added in the step of synthesizing the lipid film.

[0037] Comparative Example 2 is a blank liposome whose outer shell is modified with IR780 but which contains PFOB (hereinafter referred to as IR780-PFOB).

[0038] Table 1

[0039]

[0040] in conclusion:

[0041] (1) DPPC in comparative example 3: DSPE-PEG2000: cholesterol: mass ratio of IR780=7:1:1:18-16:2-6:2-6:1-3, in the case of PFP quantification, DPPC:DSPE-PEG2000:cholesterol When the mass ratio of :IR780>8-16:...

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Abstract

The invention belongs to the technical field of biological medicine, and particularly discloses a preparing method of a chondriosome-targeted multilayer tumor deep-penetration sound sensitizer with sound responsiveness. The method comprises the following steps of 1, synthesizing an adipose membrane with IR780; 2, hydrating the adipose membrane obtained in step 1, adding PFP, and conducting sonic vibration and centrifugation under an ice bath to prepare the sound sensitizer IR780-NDs. The sound sensitizer prepared by means of the preparing method can deeply penetrate through tumors at multiplelayers, and is uniformly distributed in the tumors.

Description

technical field [0001] The application of the present invention belongs to the technical field of biomedicine, and specifically discloses a preparation method of a mitochondria-targeted, acoustically responsive, multi-level tumor deep penetrating sonosensitizer. Background technique [0002] Mitochondria play an important role in apoptosis, programmed cell death, and the transmission of mitochondrial reactive oxygen species signals. Therefore, mitochondria are very attractive targets for anticancer drugs. [0003] Sonodynamic therapy is an alternative therapy for cancer treatment based on ultrasound (US) and sonosensitizers. Selective enrichment into tumor regions and how sonosensitizers can be delivered intravascularly to deep areas of poorly perfused tumors. Because the unique "leakage" structure of tumor blood vessels enhances the EPR effect, sonosensitizers can be passively accumulated in tumors (the more they accumulate, the more beneficial to tumor treatment), but th...

Claims

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Application Information

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IPC IPC(8): A61K41/00A61K49/22A61K49/00A61P35/00
CPCA61K41/0033A61K49/0013A61K49/0021A61K49/0078A61K49/22A61K49/222A61K49/223A61P35/00
Inventor 王冬张亮王志刚李兴升易衡静黄菊冉海涛李攀郝兰
Owner CHONGQING MEDICAL UNIVERSITY
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