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Nano co-delivery system for co-delivering NO donor and nanomedicine

A nano drug and co-delivery technology, applied in the field of biomedicine, to achieve the effects of promoting expansion, enhancing MMP expression and activity, and promoting penetration

Inactive Publication Date: 2019-03-01
SHANGHAI JIAOTONG UNIV SCHOOL OF MEDICINE
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

However, there is no report on the content of promoting the deep penetration of nano-drugs in tumor tissue by co-delivering NO donors and nano-drugs in the nano-co-delivery system of the present invention.

Method used

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  • Nano co-delivery system for co-delivering NO donor and nanomedicine
  • Nano co-delivery system for co-delivering NO donor and nanomedicine
  • Nano co-delivery system for co-delivering NO donor and nanomedicine

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0038] Example 1 Construction and characterization of the nano co-delivery system DN@MSN for the co-delivery of NO donors and DOX

[0039] 1 Purpose and principle

[0040] Design and construction of a mesoporous silica nanoparticle-based nanoco-delivery system for co-delivery of NO donors and DOX. Prepare mesoporous silica nanoparticles by solution sol method, then modify the surface with sulfhydryl groups, remove the template agent, and then use a small part of sulfhydryl groups to modify PEG, and convert most of the remaining sulfhydryl groups into nitrosothiols , and then loaded with doxorubicin, a nano co-delivery system for co-delivery of NO donor and doxorubicin was successfully prepared.

[0041] 2 methods

[0042] Weigh 0.5g cetyltrimethylammonium bromide (CTAB), put it in a 500ml round bottom flask, add 240ml triple distilled water and 1.75ml 2M NaOH, stir vigorously at 70°C until the temperature is stable for 30min, then dropwise 2.2ml tetraethyl orthosilicate (TE...

Embodiment 2

[0046] Example 2 Study on the effect of DN@MSN on the tumor microenvironment

[0047] 1 Purpose and principle

[0048] Characterize the effect of DN@MSN on the tumor microenvironment by immunofluorescence staining method, tissue western bot, and immunohistochemical experimental methods

[0049] 2 methods

[0050] (1) To study the effect of DN@MSN on the content of peroxynitrite in tumor tissue

[0051] Experimental grouping: ①MSN group; ②N@MSN group; ③DN@MSN group; ④N@MSN+uric acid (UA)

[0052] Experimental scheme: 48 hours after administration (dose 8 μmol / kg), the tumor tissue was taken out, fixed in paraformaldehyde, embedded in paraffin, and used for immunohistochemical experiment of trinitrotyrosine (3-NT), using IPP software for statistical quantification, To investigate the effect of co-delivered NO on the content of peroxynitrite in tumor tissue.

[0053] (2) Study the effect of DN@MSN on the expression and activity of matrix metalloproteinases (pro-MMP and MMPs) ...

Embodiment 3D

[0065] Implementation example 3 DN@MSN nano-co-delivery system enhances the penetration of nano-drugs in tumor tissues

[0066] 1 Purpose and principle

[0067] Immunofluorescence and small animal imaging were used to investigate the accumulation and penetration of nanomedicines in tumor tissues.

[0068] 2 methods

[0069] Model establishment: Female BALB / c mice were inoculated with 4T1 mouse breast cancer cells (8×10 5 indivual).

[0070] (1) Effect on the penetration of nano-drugs in tumor tissue

[0071] 48 hours after intravenous injection of N@MSN (NO dosage 6 μmol / kg) and MSN, intravenous injection of iF647-labeled nanoparticles, 24 hours later, the tumor tissue was taken out for immunofluorescence experiment, tumor blood vessels were labeled with CD31, and the overall fluorescence pictures of the tumor were taken. IPP software was used to count the distribution of nanoparticles in tumor tissue, and the effect of NO on the penetration ability of nanomedicine in tumo...

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Abstract

The present invention relates to a nano co-delivery system for co-delivering a NO donor and nanomedicine. The system comprises a nanocarrier, the NO donor and the nanomedicine, wherein the nanocarrieris a mesoporous silica nanoparticle, the NO donor is nitrosothiol bonded to the surface of the nanocarrier, and the nanomedicine is loaded in a mesoporous channel of the nanocarrier. The invention also relates to a preparation method of the co-delivery system and application of the co-delivery system in promoting deep permeation of the nanomedicine in tumor tissue. After intravenous administration, the nano co-delivery system is gathered in the tumor tissue through an EPR effect, nitrosothiol is decomposed to release NO, the expression and activity of MMP are improved through a process of NO,ONOO and MMP, tumor matrix collagen is degraded, the deep permeation of the nanomedicine in the tumor tissue is promoted, and an anti-tumor curative effect is improved.

Description

technical field [0001] The invention relates to the technical field of biomedicine, in particular to a nano co-delivery system for co-delivering NO donors and nano-medicines, which can promote the deep penetration of nano-medicines in tumor tissues. Background technique [0002] At present, tumor targeting therapy based on nanotechnology is a hotspot in basic and clinical research of tumors. Compared with traditional small-molecule chemotherapeutic drugs, nano-drugs can improve the solubility and chemical stability of small-molecule chemotherapeutic drugs, prolong the plasma half-life, improve pharmacokinetic behavior, and achieve targeted delivery of drugs. The pharmacological basis of nanomedicine targeted therapy for tumors is the unique "enhanced penetration and retention" effect (enhanced permeation and retention effect, ie EPR effect) of tumor tissue. Compared with normal tissues and organs, the pathophysiological characteristics of solid tumors are significantly diff...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): A61K47/52A61K47/60A61K47/69A61K9/51A61K47/04A61K47/10A61K33/00A61K31/704A61P35/00
CPCA61K9/5115A61K9/5146A61K31/704A61K33/00A61K47/52A61K47/60A61K47/6923A61P35/00A61K2300/00
Inventor 方超董霄陆琴
Owner SHANGHAI JIAOTONG UNIV SCHOOL OF MEDICINE
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