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

Abstract

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.

• Authors: Joohee Jung, Seong-Yun Jeong, Seok Soon Park, Seol Hwa Shin, Eun Jin Ju, Jinhyang Choi, Jaesook Park, Jae Hee Lee, Inki Kim, Young-Ah Suh, Jung Jin Hwang, Shun'ichi Kuroda, Jung Shin Lee, Si Yeol Song, Eun Kyung Choi
• Journal: International journal of oncology (Int J Oncol) Vol. 46 Issue 3 Pg. 1268-74 (Mar 2015) ISSN: 1791-2423 [Electronic] Greece
• PMID: 25544240 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Drug Carriers
• Liposomes
• Radiation-Sensitizing Agents
• ErbB Receptors
• Cisplatin

Topics

• Animals
• Carcinoma, Non-Small-Cell Lung (pathology, therapy)
• Chemoradiotherapy (methods)
• Cisplatin (administration & dosage, adverse effects)
• Drug Carriers
• ErbB Receptors (antagonists & inhibitors)
• Humans
• Kidney Diseases (chemically induced, prevention & control)
• Liposomes
• Lung Neoplasms (pathology, therapy)
• Mice
• Mice, Inbred BALB C
• Mice, Nude
• Molecular Targeted Therapy (methods)
• Radiation Injuries (prevention & control)
• Radiation-Sensitizing Agents (administration & dosage, adverse effects)
• Treatment Outcome
• Tumor Cells, Cultured
• Xenograft Model Antitumor Assays