title: Systemic delivery and preclinical evaluation of Au nanoparticle containing beta-lapachone for radiosensitization.
abstract: 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 ss-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.
authors.affiliation: Institute for Innovative Cancer Research, Asan Medical Center, Seoul, 138-736, Republic of Korea.
authors.forename: Seong-Yun
authors.initials: SY
authors.lastname: Jeong
authors.forename: Sung-Jin
authors.initials: SJ
authors.lastname: Park
authors.forename: Sang Min
authors.initials: SM
authors.lastname: Yoon
authors.forename: Joohee
authors.initials: J
authors.lastname: Jung
authors.forename: Ha Na
authors.initials: HN
authors.lastname: Woo
authors.forename: So Lyoung
authors.initials: SL
authors.lastname: Yi
authors.forename: Si Yeol
authors.initials: SY
authors.lastname: Song
authors.forename: Heon Joo
authors.initials: HJ
authors.lastname: Park
authors.forename: Chulhee
authors.initials: C
authors.lastname: Kim
authors.forename: Jin Seong
authors.initials: JS
authors.lastname: Lee
authors.forename: Jung Shin
authors.initials: JS
authors.lastname: Lee
authors.forename: Eun Kyung
authors.initials: EK
authors.lastname: Choi
mesh_terms: D000818:Animals; D000911:Antibodies, Monoclonal / Q000737:chemistry / Q000378:metabolism; D001692:Biological Transport; D045744:Cell Line, Tumor; D002470:Cell Survival; D002626:Chemistry, Pharmaceutical; D004337:Drug Carriers; D004339:Drug Compounding; D004353:Drug Evaluation, Preclinical; D066246:ErbB Receptors / Q000378:metabolism; D006046:Gold / Q000737:chemistry*; D006801:Humans; D007275:Injections, Intravenous; D008175:Lung Neoplasms / Q000378:metabolism / Q000473:pathology / Q000532:radiotherapy*; D053768:Metal Nanoparticles; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D009285:Naphthoquinones / Q000008:administration & dosage* / Q000737:chemistry; D011838:Radiation-Sensitizing Agents / Q000008:administration & dosage* / Q000737:chemistry; D015203:Reproducibility of Results; D013997:Time Factors; D023041:Xenograft Model Antitumor Assays
chemical_list: D000911:Antibodies, Monoclonal; D004337:Drug Carriers; D009285:Naphthoquinones; D011838:Radiation-Sensitizing Agents; C014638:beta-lapachone; D006046:Gold; C512478:EGFR protein, human; D066246:ErbB Receptors