期刊
JOURNAL OF CONTROLLED RELEASE
卷 139, 期 3, 页码 239-245出版社
ELSEVIER SCIENCE BV
DOI: 10.1016/j.jconrel.2009.07.007
关键词
Au; Nanoparticle; Lapachone; Delivery; Radiosensitization
资金
- Korea Health 21 RD Project [A062254]
- Ministry of Health, Welfare and Family affairs, Republic of Korea
- Ministry of Education, Science and Technology of Korea [2008-03876]
- National Research Foundation of Korea [2008-03876] Funding Source: Korea Institute of Science & Technology Information (KISTI), National Science & Technology Information Service (NTIS)
Effective delivery of radiosensitizer to target tumor cells, causing preferentially increased tumor cytotoxicity, while simultaneously minimizing damage to healthy cells around the tumor, is an ideal strategy for the improvement of radiotherapeutic efficacy against human cancer. We aimed to enhance radiotherapeutic efficacy by using biocompatible gold nanoparticles (AuNP) as a vehicle for systemic delivery of beta-lapachone (lap). Lap is a novel anticancer agent displaying potent cytotoxicity against cancer cells expressing NAD(P)H: quinone oxidoreductase-1 enzyme (NQO1). Although lap is expected to be a very promising radiosensitizer, its poor solubility and non-specific distribution obstruct preclinical evaluation and clinical application. In this study, the property of AuNPs carrying lap (AuNPs/lap) for active-targeting tumor cells and improving in vivo radiotherapeutic efficacy was evaluated. Murine monoclonal anti-EGFR antibody was conjugated to the AuNPs/lap as a ligand for active targeting. The active tumor-targeting property of AuNPs/lap conjugating anti-EGFR antibody was validated in vitro experiments using cell lines expressing EGFR at different levels. In mice bearing xenograft human tumors, the intravenous injection of AuNPs/lap exhibited highly enhanced radiotherapeutic efficacy. AuNPs/lap offers a new modality for improvement of radiotherapeutic efficacy and feasibility of further clinical application for human cancer treatment. (C) 2009 Elsevier B.V.Elsevier All rights reserved.
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