Cascade-Targeting of Charge-Reversal and Disulfide Bonds Shielding for Efficient DOX Delivery of Multistage Sensitive MSNs-COS-SS-CMC

Overview

Journal Int J Nanomedicine

Publisher Dove Medical Press

Specialty Biotechnology

Date 2020 Sep 5

PMID 32884269

Citations 2

Authors

Lan Cui

Wentao Liu

Hao Liu

Qian Qin

Shuangxia Wu

Suqin He

Zhenya Zhang

Xinchang Pang

Chengshen Zhu

Affiliations

Soon will be listed here.

Abstract

Background: Although pH and redox sensitiveness have been extensively investigated to improve therapeutic efficiency, the effect of disulfide bonds location and pH-triggered charge-reversal on cascade-targeting still need to be further evaluated in cancer treatment with multi-responsive nanoparticles.

Purpose: The aim of this study was to design multi-responsive DOX@MSNs-COS-NN-CMC, DOX@MSNs-COS-SS-CMC and DOX@MSNs-COS-CMC-SS and systematically investigate the effects of disulfide bonds location and charge-reversal on the cancer cell specificity, endocytosis mechanisms and antitumor efficiency.

Results: In vitro drug release rate of DOX@MSNs-COS-SS-CMC in tumor environments was 7-fold higher than that under normal physiological conditions after 200 h. Furthermore, the fluorescence intensity of DOX@MSNs-COS-SS-CMC and DOX@MSNs-COS-CMC-SS was 1.9-fold and 1.3-fold higher than free DOX at pH 6.5 and 10 mM GSH. In addition, vesicular transport might be a factor that affects the uptake efficiency of DOX@MSNs-COS-SS-CMC and DOX@MSNs-COS-CMC-SS. The clathrin-mediated endocytosis and endosomal escape of DOX@MSNs-COS-SS-CMC enhanced cellular internalization and preserved highly controllable drug release into the perinuclear of HeLa cells. DOX@MSNs-COS-SS-CMC exhibited a synergistic chemotherapy in preeminent tumor inhibition and less side effects of cardiotoxicity.

Conclusion: The cascade-targeting of charge-reversal and disulfide bonds shielding would be a highly personalized strategy for cervical cancer treatment.

Citing Articles

Strategies to Regulate the Degradation and Clearance of Mesoporous Silica Nanoparticles: A Review.

Zhang Y, Lin X, Chen X, Fang W, Yu K, Gu W Int J Nanomedicine. 2024; 19:5859-5878.

PMID: 38887691 PMC: 11182361. DOI: 10.2147/IJN.S451919.

Charge reversal nano-systems for tumor therapy.

Zhang P, Chen D, Li L, Sun K J Nanobiotechnology. 2022; 20(1):31.

PMID: 35012546 PMC: 8751315. DOI: 10.1186/s12951-021-01221-8.

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