PH-responsive multifunctional nano drug carrier and application in skin diseases thereof

A nano-drug loading and multifunctional technology, applied in the field of biomedicine, can solve the problems of different release rates of doxorubicin and affect the therapeutic effect, etc., achieve the effects of inhibiting tumor growth and metastasis, improving clinical efficacy, and being easy to popularize and apply

Pending Publication Date: 2020-03-31
XIEHE HOSPITAL ATTACHED TO TONGJI MEDICAL COLLEGE HUAZHONG SCI & TECH UNIV
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

However, the doxorubicin (DOX) loading of zinc oxide quantum dots (ZnO QDs) is only 20%, and the release rate of doxorubicin (DOX) is different at different pHs, which greatly affects the therapeutic effect.

Method used

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  • PH-responsive multifunctional nano drug carrier and application in skin diseases thereof
  • PH-responsive multifunctional nano drug carrier and application in skin diseases thereof
  • PH-responsive multifunctional nano drug carrier and application in skin diseases thereof

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0028] The multifunctional nano drug carrier loaded with doxorubicin, the specific preparation method is as follows:

[0029] 1) Mesoporous silica-coated gold nanospheres (AuNP@mSiO 2 ) a drug carrier with a "core-shell" structure;

[0030] 2) Preparation of water-soluble ZnO quantum dots (ZnO QDs or ZnO-NH 2 );

[0031] 3) Add TESPA ethanol solution to the drug carrier prepared in step 1) to prepare carboxylated AuNP@mSiO 2 ;

[0032] 4) To the AuNP@mSiO prepared in step 3) 2 - Add doxorubicin (DOX) aqueous solution to the COOH aqueous solution, and stir in the dark for 24 hours, and realize the loading of doxorubicin (DOX) by utilizing the porous structure of mesoporous silica;

[0033] 5) To the DOX-loaded AuNP@mSiO prepared in step 4) 2 -Add EDC·HCl and NHS to COOH to activate the carboxyl groups, then add the ZnOQDs prepared in step 2), and assemble the above drug-loaded nanoparticles through electrostatic interaction to obtain a pH-responsive nanoparticle with gold...

Embodiment 2

[0036] AuNP@mSiO 2 Application of @DOX-ZnO in inhibiting the growth and lung metastasis of melanoma

[0037] 1) The in vivo experiments were grouped as follows: PBS, PBS+NIR, DOX, AuNP@mSiO 2 -ZnO, AuNP@mSiO 2 @DOX-ZnO, AuNP@mSiO 2-ZnO+NIR, AuNP@mSiO 2 @DOX-ZnO+NIR, the light group adopts 655nm laser irradiation (1.0W / cm 2 , 40s). One treatment every 3 days, a total of 3 treatments. The next day, the tumor length and width were recorded with a vernier caliper, and the tumor volume was calculated;

[0038] 2) From the first treatment to the 16th day after the treatment, the experiment was terminated, the tumor weight was measured, and the tumor and lung tissues of the mice were collected for HE and Ki-67 immunohistochemical staining.

[0039] The experimental results show that despite the low irradiation power and treatment time, AuNP@mSiO 2 @DOX-ZnO can effectively inhibit tumor growth (such as image 3 shown) and lung metastases (as shown Figure 4 shown).

Embodiment 3

[0041] The multifunctional nano drug carrier loaded with interferon, the specific preparation method is as follows:

[0042] 1) Mesoporous silica-coated gold nanospheres (AuNP@mSiO 2 ) a drug carrier with a "core-shell" structure;

[0043] 2) Preparation of water-soluble ZnO quantum dots (ZnO QDs or ZnO-NH 2 );

[0044] 3) Add TESPA ethanol solution to the drug carrier prepared in step 1) to prepare carboxylated AuNP@mSiO 2 ;

[0045] 4) To the AuNP@mSiO prepared in step 3) 2 -Interferon (IFN)-γ aqueous solution was added to the COOH aqueous solution, and stirred for 24 hours in the dark, and the porous structure of mesoporous silica was used to realize the loading of IFN;

[0046] 5) To the IFN-loaded AuNP@mSiO prepared in step 4) 2 -Add EDC·HCl and NHS to COOH to activate the carboxyl group, then add the ZnOQDs prepared in step 2), and assemble the above-mentioned drug-loaded nanoparticles through electrostatic interaction to obtain pH-responsive nanoparticles with gol...

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Abstract

The invention discloses a pH-responsive multifunctional nano drug carrier and an application in skin diseases thereof. The carrier uses a mesoporous silica-coated gold nanoparticle core-shell structure as a drug carrier, the drug carrier is first subjected to carboxylation with a TESPA ethanol solution, then a drug aqueous solution is added into a carboxylated drug carrier aqueous solution, a porous structure of mesoporous silica is used to realize loading of a drug, then EDC.HC1 and NHS are added to activate the carboxyl group, finally a zinc oxide quantum dot pore-blocking agent is added, and the above-mentioned drug-loaded nanoparticles are assembled by electrostatic action. The multifunctional nano drug carrier realizes the comprehensive combination of targeted drug delivery, photo-thermal therapy, chemotherapy and immunotherapy, and is applied to treat skin tumors and viral infectious skin diseases. In addition, a drug loading rate is increased to (33.89+ / -1.64)%, the clinical efficacy is improved, and shortcomings of current traditional treatment and emerging immunotherapy are made up.

Description

technical field [0001] The invention belongs to the technical field of biomedicine, and in particular relates to a pH-responsive multifunctional nano drug carrier and its application in skin diseases. Background technique [0002] Malignant skin tumors, especially malignant melanoma, are highly malignant and prone to early metastasis, and the 5-year survival rate of advanced melanoma patients with distant metastasis is less than 5%. Traditional surgery, radiotherapy and chemotherapy are invasive, poor curative effect, difficult to locate and have obvious toxic and side effects. Although current targeted molecular therapies (such as BRAF and MEK inhibitors) and immune checkpoint inhibitors (such as anti-CTLA-4 and anti-PD-1 monoclonal antibodies) can improve the overall survival rate of melanoma patients, some patients Easy to drug resistance and recurrence, still can not effectively control tumor metastasis and disease progression, treatment-related side effects increased s...

Claims

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Application Information

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IPC IPC(8): A61K41/00A61K31/704A61K38/21A61K45/00A61K47/02A61K47/69A61P17/00A61P31/12A61P35/00A61P35/04
CPCA61K31/704A61K38/21A61K41/0052A61K45/00A61K47/02A61K47/6949A61P17/00A61P31/12A61P35/00A61P35/04A61K2300/00
Inventor 陶娟张亚敏朱锦涛郭晨刘丽萍李钰策
Owner XIEHE HOSPITAL ATTACHED TO TONGJI MEDICAL COLLEGE HUAZHONG SCI & TECH UNIV
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