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 Supplementary Materials and Methods
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.
