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In vitro evaluation of folic acid-conjugated redox-responsive mesoporous silica nanoparticles for the delivery of cisplatin

Authors Alvarez-Berríos MP, Vivero-Escoto JL

Received 26 July 2016

Accepted for publication 24 September 2016

Published 23 November 2016 Volume 2016:11 Pages 6251—6265

DOI https://doi.org/10.2147/IJN.S118196

Checked for plagiarism Yes

Review by Single-blind

Peer reviewers approved by Dr Akshita Wason

Peer reviewer comments 2

Editor who approved publication: Professor Carlos Rinaldi

Merlis P Alvarez-Berríos,1 Juan L Vivero-Escoto2,3

1Department of Science and Technology, Inter American University of Puerto Rico, Ponce, Puerto Rico, 2Department of Chemistry, 3Center for Biomedical Engineering and Science, University of North Carolina at Charlotte, Charlotte, NC, USA

Abstract: The use of cisplatin(IV) prodrugs for the delivery of cisplatin have gained significant attention, because of their low toxicity and reactivity. Recent studies have shown that targeted cisplatin(IV)-prodrug nanoparticle-based delivery systems can improve the internalization of the cisplatin(IV) prodrug. We hypothesized that folic acid-conjugated mesoporous silica nanoparticles (MSNs) containing cisplatin(IV) prodrug could target cancer cells that overexpress the folate receptor and deliver the active cisplatin drug upon intracellular reduction. To prove this hypothesis, internalization and localization studies in HeLa cancer cells were performed using flow cytometry and confocal microscopy. The ability of MSNs to escape from the endolysosomal compartments, the formation of DNA adducts, and the cytotoxic effects of the MSNs were also evaluated. Our results confirmed that this MSN-based delivery platform was capable of delivering cisplatin into the cytosol of HeLa cells, inducing DNA adducts and subsequent cell death.

Keywords: cancer treatment, cisplatin prodrug, intracellular delivery, folic acid, mesoporous silica

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