Biodegradable nanocarriers based on chitosan-modified mesoporous silica nanoparticles for delivery of methotrexate for application in breast cancer treatment

Zahra Shakeran; Mehrnaz Keyhanfar; Jaleh Varshosaz; Duncan S Sutherland

doi:10.1016/j.msec.2020.111526

Biodegradable nanocarriers based on chitosan-modified mesoporous silica nanoparticles for delivery of methotrexate for application in breast cancer treatment

Mater Sci Eng C Mater Biol Appl. 2021 Jan:118:111526. doi: 10.1016/j.msec.2020.111526. Epub 2020 Sep 18.

Authors

Zahra Shakeran¹, Mehrnaz Keyhanfar², Jaleh Varshosaz³, Duncan S Sutherland⁴

Affiliations

¹ Department of Biotechnology, Faculty of Biological Science and Technology, University of Isfahan, Isfahan, Iran.
² Department of Biotechnology, Faculty of Biological Science and Technology, University of Isfahan, Isfahan, Iran. Electronic address: m.keyhanfar@ast.ui.ac.ir.
³ Department of Pharmaceutics, School of Pharmacy and Novel Drug Delivery Systems Research Center, Isfahan University of Medical Sciences, Isfahan, Iran.
⁴ iNANO Interdisciplinary Nanoscience Center, Aarhus University, Gustav Wieds Vej 14, 8000 Aarhus C, Denmark.

PMID: 33255079
DOI: 10.1016/j.msec.2020.111526

Abstract

Nanocarriers have demonstrated great promise in the delivery of hydrophobic drugs particularly to tumor spaces by enhanced permeability and retention (EPR) effects. Mesoporous silica nanoparticles (MSNs) are the attractive nanocarrier system to reduce the drug's toxic side effects, enable controlled drug release, prevent drug degradation and provide a biocompatible and biodegradable high surface area carrier. Surface-modified MSNs have been applied to increase drug loading and efficiency. In this study, functionalized MSNs loaded with methotrexate (MTX) were designed for use as a cytotoxic agent. The MSNs were first modified with 3-triethoxysilylpropylamine (APTES) and then with chitosan through covalent coupling mediated by glutaraldehyde. The physicochemical properties of the nanoparticles were optimized for each step. The loading percentage (12.2%) and release profile of MTX as an anti-breast cancer drug, loaded at amine-modified MSNs, were measured via high performance liquid chromatography (HPLC). Moreover, the uptake profiles of fluorescein isothiocyanate (FITC)-labeled MSN-APTES-chitosan with or without MTX were monitored on MCF7 cancer cells via confocal microscopy. Following exposure of nanoparticles to body fluids, they were surrounded by specific proteins that may affect their cellular uptake. Hence, the adsorption profiles of protein corona on the surface of MSN, amine-modified MSN and MTX-loaded MSN-APTES-chitosan were analyzed. The cytotoxic potential for killing breast cancer cells was also studied. The MTX loaded MSN-APTES-chitosan showed a positive effect at a low dose (0.5 μM MTX). In this study, we introduce a new method to synthesize biodegradable MSNs with small and uniform particle size, achieve high MTX loading via covalent amine and chitosan-functionalization, monitor the cellular uptake and demonstrate the potential to decrease the viability of breast cancer cells at low dose.

Keywords: 3-triethoxysilylpropylamine; Breast cancer cells; Chitosan; Mesoporous silica nanoparticle; Methotrexate; Protein corona.

MeSH terms

Breast Neoplasms* / drug therapy
Chitosan*
Drug Delivery Systems
Humans
Methotrexate / pharmacology
Nanoparticles*
Porosity
Silicon Dioxide

Substances

Silicon Dioxide
Chitosan
Methotrexate