期刊
BIOMATERIALS
卷 34, 期 29, 页码 7106-7116出版社
ELSEVIER SCI LTD
DOI: 10.1016/j.biomaterials.2013.04.067
关键词
Targeted nanodrug delivery; Selenium nanoparticles; Transferrin; Apoptosis
资金
- National Science and Technology support program, Natural Science Foundation of China and Guangdong Province
- Program for New Century Excellent Talents in University
- Research Fund for the Doctoral Program of Higher Education of China
- Fundamental Research Funds for the Central Universities
- China Postdoctoral Science Foundation
Selenium nanoparticles (SeNPs) have garnered a great deal of attention as potential cancer therapeutic payloads. However, the in vivo targeting drug delivery has been challenging. Herein, we describe the synthesis of tansferrin (Tf)-conjugated SeNPs and its use as a cancer-targeted drug delivery system to achieve enhanced cellular uptake and anticancer efficacy. Tf as targeting ligand significantly enhances the cellular uptake of doxorubicin (DOX)-loaded SeNPs through clathrin-mediated and caveolae/lipid raft-mediated endocytosis in cancer cells overexpressing transferrin receptor, and increases their selectivity between cancer and normal cells. DOX-loaded and Tf-conjugated SeNPs (Tf-SeNPs) exhibits unprecedented enhanced cytotoxicity toward cancer cells through induction of apoptosis with the involvement of intrinsic and extrinsic pathways. Internalized Tf-SeNPs triggers intracellular ROS overproduction, thus activates p53 and MAPKs pathways to promote cell apoptosis. In the nude mice xenograft experiment, Tf-SeNPs significantly inhibits the tumor growth via induction of p53-mediated apoptosis. This cancer-targeted design of SeNPs opens a new path for synergistic treating of cancer with higher efficacy and decreased side effects. (C) 2013 Elsevier Ltd. All rights reserved.
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