Abstract LB-15: Enhancement of radiotherapeutic efficacy by cisplatin-incorporated bionanocapsule without nephrotoxicity

Proceedings: AACR Annual Meeting 2014; April 5-9, 2014; San Diego, CA Radiotherapy is one of the most effective tools in the clinical treatment for many types of solid tumors, but the therapeutic efficacy is often limited because of resistance to ionizing radiation. Although cisplatin (CDDP) is widely used as a radiosensitizer to improve therapeutic outcomes, its side effect such as acute nephrotoxicity limits application. To overcome the hurdle of CDDP, it is extremely necessary to apply a delivery system that can enhance the radiotherapeutic efficacy and reduce CDDP-induced side effects. Bionanocapsule (BNC) consisting of hepatitis B virus surface antigen (HBsAg) L protein is approximately 50-nm hollow particles displaying a human hepatocyte-recognizing molecule (pre-S1 peptide). BNC-liposome complex has been developed suitable to deliver drugs and genes to human hepatocytes specifically in vivo . Utilizing the character of BNC targeting hepatocytes and its property to carry anti-cancer agents, we designed a BNC complex incorporating liposomal CDDP (BNC-LP-CDDP) for hepatocellular carcinoma (HCC). HCC is the fifth most common cancer and the third most common cause of cancer related death worldwide. Although surgical resection is the optimal treatment approach, only a small proportion of patients are qualified for surgery and there is a high rate of tumor recurrence. BNC-LP-CDDP has been produced to destroy HCC without nephrotoxicity, and we aimed in this study to confirm the effect enhancing the radiotherapeutic efficacy in vitro and in vivo . The in vitro HCC-specific cytotoxicity of BNC-LP-CDDP was confirmed by comparison between human HCC Hep3B and human NSCLC A549 cells. The result of clonogenic assay to evaluate chemoradiotherapeutic efficacy of BNC-LP-CDDP demonstrated that survival fraction of hep3B showed radiosensitivity efficacy by BNC-LP-CDDP with IR. In vivo , treatment with BNC-LP-CDDP (2 mg/kg) and IR (3 Gy) delayed tumor growth accompanying increased apoptotic cell death more than that of other groups. Furthermore, BNC-LP-CDDP displayed decreased nephrotoxicity of CDDP. Collectively, our results demonstrate that BNC-LP-CDDP in combination with ionizing radiation enhanced radiotherapeutic efficacy by human liver-pinpoint delivery and eliminated CDDP-induced nephrotoxicity. Citation Format: Seol Hwa Shin, Seok Soon Park, Joohee Jeong, Jinhyang Choi, Jaesook Park, Jae Hee Lee, Hye Ji Park, Si Yeol Song, Seong-Yun Jeong, Shun'ich Kuroda, Eun Kyung Choi. Enhancement of radiotherapeutic efficacy by cisplatin-incorporated bionanocapsule without nephrotoxicity. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr LB-15. doi:10.1158/1538-7445.AM2014-LB-15