期刊
BIOMATERIALS
卷 35, 期 1, 页码 316-326出版社
ELSEVIER SCI LTD
DOI: 10.1016/j.biomaterials.2013.09.098
关键词
Anti-tumor activity; Apoptotic cell death; Bortezomib; Drug delivery; Mesoporous silica; NSCLC
资金
- National Science Foundation of China [31270828, 31070678]
- Ministry of Science and Technology, China [2010CB912101, 2012CB910800, 2013CB910900, 2011CB915501]
- Sanofi-aventis SIBS Young Investigator award
- Cancer Center of Xuhui Central Hospital [CCR2012003]
- Shanghai Institute of Neurosciences
- Shanghai Municipal Department of Science and Technology [PJ[2010]00123]
- Wuzhong Biomedical Center of Suzhou, Jiangshu, Chinese Academy of Sciences
Bortezomib (BTZ) is the first clinically approved proteasome inhibitor for treating multiple human malignancies. However, the poor water-solubility and low stability of BTZ and the emergence of tumor resistance have severely restrained its therapeutic efficacy. Herein, we report the application of hollow mesoporous silica nanospheres (HMSNs) in encapsulating BTZ for drug delivery. In in vitro cell viability assay on human NSCLC H1299 cells, the half-maximum inhibiting concentration (IC50) of HMSNs-BTZ was 42% of that for free BTZ in 48 h treatments. In vivo tumor-suppression assay further indicated that HMSNs-BTZ (0.3 mg/kg) showed approximately 1.5 folds stronger anti-tumor activity than free BTZ. Furthermore, we report that more potent induction of cell cycle arrest and apoptotic cell death, along with promoted activation of Caspase 3 and autophagy might mechanistically underlie the improved antitumor efficacy of HMSNs-BTZ. Finally, the tumor-suppressing effect of HMSNs-BTZ was enhanced in the presence of wild-type p53 signaling, suggesting a potential enhancement in clinical efficacy with combined p53 gene therapy and BTZ-based chemotherapy. Therefore, the HMSNs-based nanoparticles are emerging as a promising platform to deliver therapeutic agents for beneficial clinical outcomes through lowering doses and frequency of drug administration and reducing potential side effects. (C) 2013 Elsevier Ltd. All rights reserved.
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