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Polyaspartic acid-anchored mesoporous silica nanoparticles for pH-responsive doxorubicin release

Authors Hakeem A, Zahid F, Zhan G, Yi P, Yang H, Gan L, Yang X

Received 21 July 2017

Accepted for publication 7 December 2017

Published 19 February 2018 Volume 2018:13 Pages 1029—1040

DOI https://doi.org/10.2147/IJN.S146955

Checked for plagiarism Yes

Review by Single-blind

Peer reviewers approved by Dr Alexander Kharlamov

Peer reviewer comments 3

Editor who approved publication: Dr Linlin Sun


Abdul Hakeem,1,2,* Fouzia Zahid,1,* Guiting Zhan,1 Ping Yi,3 Hai Yang,1 Lu Gan,1 Xiangliang Yang1

1National Engineering Research Center for Nanomedicine, Department of Nanomedicine and Biopharmaceuticals, College of Life Science and Technology, Huazhong University of Science and Technology, Wuhan, People’s Republic of China; 2Faculty of Marine Sciences, Lasbela University of Agriculture, Water and Marine Sciences, Uthal, Pakistan; 3Department of Biophysics and Molecular Physiology, College of Life Science and Technology, Huazhong University of Science and Technology, Wuhan, People’s Republic of China

*
These authors contributed equally to this work

Background: Nanotechnology-based drug delivery systems exhibit promising therapeutic efficacy in cancer chemotherapy. However, ideal nano drug carriers are supposed to be sufficiently internalized into cancer cells and then release therapeutic cargoes in response to certain intracellular stimuli, which has never been an easy task to achieve.
Objective: This study is to design mesoporous silica nanoparticles (MSNs)-based pH-responsive nano drug delivery system that is effectively internalized into cancer cells and then release drug in response to lysosomal/endosomal acidified environment.
Methods: We synthesized MSNs by sol-gel method. Doxorubicin (DOX) was encapsulated into the pores as a model drug. Polyaspartic acid (PAsA) was anchored on the surface of mesoporous MSNs (P-MSNs) as a gatekeeper via amide linkage and endowed MSNs with positive charge.
Results: In vitro release analysis demonstrated enhanced DOX release from DOX-loaded PAsA-anchored MSNs (DOX@P-MSNs) under endosomal/lysosomal acidic pH condition. Moreover, more DOX@P-MSNs were internalized into HepG2 cells than DOX-loaded MSNs (DOX@MSNs) and free DOX revealed by flow cytometry. Likewise, confocal microscopic images revealed that DOX@P-MSNs effectively released DOX and translocated to the nucleus. Much stronger cytotoxicity of DOX@P-MSNs against HepG2 cells was observed compared with DOX@MSNs and free DOX.
Conclusion: DOX@P-MSNs were successfully fabricated and achieved pH-responsive DOX release. We anticipated this nanotherapeutics might be suitable contenders for future in vivo cancer chemotherapeutic applications.

Keywords: cancer chemotherapy, mesoporous silica nanoparticles, polyaspartic acid, pH-responsive release, cytotoxicity

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