期刊
BIOMATERIALS
卷 39, 期 -, 页码 23-30出版社
ELSEVIER SCI LTD
DOI: 10.1016/j.biomaterials.2014.10.069
关键词
Drug delivery; Platinum; Micelle; Nanoparticle; Chemotherapy
资金
- Japan Society for the Promotion of Science (JSPS)
- Japanese Ministry of Health, Labor, and Welfare (MHLW)
- Ministry of Education, Culture, Sports, Science and Technology (MEXT)
- Challenging Exploratory Research [24659584]
- Initiative for Accelerating Regulatory Science in Innovative Drug, Medical Device, and Regenerative Medicine
- National Cancer Center Research and Development Fund
- Health and Labour Sciences Research Grants (Clinical Trial on Development of New Drugs and Medical Devices)
- [23700526]
- [25750172]
- [24689051]
- Grants-in-Aid for Scientific Research [24659584, 25670010, 24689051, 23390009, 25750172] Funding Source: KAKEN
Antibody-mediated therapies including antibody-drug conjugates (ADCs) have shown much potential in cancer treatment by tumor-targeted delivery of cytotoxic drugs. However, there is a limitation of pay-loads that can be delivered by ADCs. Integration of antibodies to drug-loaded nanocarriers broadens the applicability of antibodies to a wide range of therapeutics. Herein, we developed antibody fragment-installed polymeric micelles via maleimide-thiol conjugation for selectively delivering platinum drugs to pancreatic tumors. By tailoring the surface density of maleimide on the micelles, one tissue factor (TF)-targeting Fab' was conjugated to each carrier. Fab'-installed platinum-loaded micelles exhibited more than 15-fold increased cellular binding within 1 h and rapid cellular internalization compared to non-targeted micelles, leading to superior in vitro cytotoxicity. In vivo, Fab'-installed micelles significantly suppressed the growth of pancreatic tumor xenografts for more than 40 days, outperforming non-targeted micelles and free drugs. These results indicate the potential of Fab'-installed polymeric micelles for efficient drug delivery to solid tumors. (C) 2014 Elsevier Ltd. All rights reserved.
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