A cisplatin-incorporated liposome that targets the epidermal growth factor receptor enhances radiotherapeutic efficacy without nephrotoxicity

作者：Jung Joohee; Jeong Seong Yun; Park Seok Soon; Shin Seol Hwa; Ju Eun Jin; Choi Jinhyang; Park Jaesook; Lee Jae Hee; Kim Inki; Suh Young Ah; Hwang Jung Jin; Kuroda Shun'ichi; Lee Jung Shin; Song Si Yeol; Choi Eun Kyung^*

来源：International Journal of Oncology, 2015, 46(3): 1268-1274.

DOI：10.3892/ijo.2014.2806

• cisplatin
• liposome
• epidermal growth factor receptor antibody
• drug delivery system
• radiotherapy
• non-small cell lung cancer

Radiotherapy (RT) is one of the major modalities for non-small cell lung cancer (NSCLC), but its efficacy is often compromised by cellular resistance caused by various mechanisms including the overexpression of epidermal growth factor receptor (EGFR). Although cis-diamminedichloroplatinum(II) (cisplatin, CDDP) has been well characterized as an effective radiosensitizer, its clinical application is limited by its severe nephrotoxic effects. In our current study, we developed a CDDP-incorporated liposome (LP) conjugated with EGFR antibodies (EGFR:LP-CDDP) and evaluated its potential to radiosensitize EGFR-overexpressing cells without exerting nephrotoxic effects. EGFR:LP-CDDP showed higher cytotoxicity than non-targeting liposomal CDDP (LP-CDDP) in the cells expressing EGFR in vitro. In an A549 cell-derived xenograft tumor mouse model, increased delays in tumor growth were observed in the mice treated with a combination of EGFR:LP-CDDP and radiation. Notably, the EGFR:LP-CDDP-treated animals showed no differences in body weight loss, survival rates of nephrotoxicity compared with untreated control mice. In contrast, the use of CDDP caused lower body weights and poorer survival outcomes accompanied by a significant level of nephrotoxicity [e.g., decreased kidney weight, increased blood urea nitrogen (BUN) and creatinine, and pathological change]. These findings suggest the feasibility of using EGFR:LP-CDDP to radiosensitize cells in a targeted manner without inducing nephrotoxic effects. This compound may therefore have clinical potential as part of a tailored chemoradiotherapy strategy.

• 出版日期2015-3