journal contribution
posted on 2023-03-31, 00:24 authored by Mingzhen Zhang, Changlong Xu, Liuqing Wen, Moon Kwon Han, Bo Xiao, Jun Zhou, Yuchen Zhang, Zhan Zhang, Emilie Viennois, Didier Merlin Adsorption/desorption isotherms and pore size distributions of MSN-NH2 (S1). FITR spectra of MSN-NH2 and MSN-destriobiotin (S2). DLS and TEM characterizations of MSN-HA/Dox (S3). Figures of MSN-HA loaded with rhodamine B (S4). Release profiles of Dox in MSN-HA/Dox under neutral buffer (pH 7.0) (S5). The co-localization of MSN-HA/rhodamine B with the endocytosis marker (S6). In vitro compatibilities investigated by MTT and ATPlite assays (S7). In vivo biocompatibility evaluation of MSN-HA (S8). Fluorescence images of Colon-26 and HT-29 cells incubated with Dox and MSN-HA/Dox (S9). MSN-HA/Dox induced apoptosis in vitro (S10). Interaction of MSN-HA with proteins and blood cells (S11). Immunological analysis of MSN-HA and MSN-HA/Dox (S12). Histological analysis of tumor tissues (S13). Times-dependent biodistribution of MSN-HA (S14).
Funding
U.S. Department of Veterans Affairs
National Institute of Diabetes and Digestive and Kidney Diseases
Crohn's and Colitis Foundation of America
History
ARTICLE ABSTRACT
The ability of nanoparticles to target tumors and to enable site-specific drug release provides a unique system for the delivery of effective therapy with reduced toxic side effects. In this study, we used mesoporous silica nanoparticles (MSN) to fabricate a targeted drug delivery system that is responsive to hyaluronidase (HAase). Following engraftment of desthiobiotin onto the surface of MSN, a streptavidin complex was generated, which was functionalized with biotin-modified hyaluronic acid (HA) to enable controlled drug release at cancer cells expressing HAase. Various technologies were used to confirm the successful fabrication of this MSN-based nanocarrier system for targeted drug delivery. In vitro analyses showed that the release of doxorubicin hydrochloride (Dox) was accelerated significantly in the presence of biotin or HAase and accelerated further in the presence of biotin and HAase. Uptake by cancer cells was mediated efficiently by CD44 receptor–mediated endocytosis and the MSN exhibited good biocompatibility in vitro and in vivo. MSN-HA/Dox nanoparticles induced apoptosis in cancer cells more efficiently than free doxorubicin and inhibited tumor growth with minimal systemic toxicity in vivo. Collectively, our findings offered a preclinical proof of concept for a novel targeted drug delivery carrier system for cancer therapy. Cancer Res; 76(24); 7208–18. ©2016 AACR.
