TY - JOUR
T1 - Biodegradable nanocarriers based on chitosan-modified mesoporous silica nanoparticles for delivery of methotrexate for application in breast cancer treatment
AU - Shakeran, Zahra
AU - Keyhanfar, Mehrnaz
AU - Varshosaz, Jaleh
AU - Sutherland, Duncan S.
PY - 2021/1
Y1 - 2021/1
N2 - 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.
AB - 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.
KW - 3-triethoxysilylpropylamine
KW - Breast cancer cells
KW - Chitosan
KW - Mesoporous silica nanoparticle
KW - Methotrexate
KW - Protein corona
UR - http://www.scopus.com/inward/record.url?scp=85092065794&partnerID=8YFLogxK
U2 - 10.1016/j.msec.2020.111526
DO - 10.1016/j.msec.2020.111526
M3 - Article
C2 - 33255079
AN - SCOPUS:85092065794
SN - 0928-4931
VL - 118
JO - Materials Science and Engineering C
JF - Materials Science and Engineering C
M1 - 111526
ER -