title: 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.affiliation: Institute for Innovative Cancer Research, Asan Medical Center, University of Ulsan College of Medicine, Seoul 138‑736, Republic of Korea.
authors.forename: Joohee
authors.initials: J
authors.lastname: Jung
authors.affiliation: Institute for Innovative Cancer Research, Asan Medical Center, University of Ulsan College of Medicine, Seoul 138‑736, Republic of Korea.
authors.forename: Seong-Yun
authors.initials: SY
authors.lastname: Jeong
authors.affiliation: Institute for Innovative Cancer Research, Asan Medical Center, University of Ulsan College of Medicine, Seoul 138‑736, Republic of Korea.
authors.forename: Seok Soon
authors.initials: SS
authors.lastname: Park
authors.affiliation: Institute for Innovative Cancer Research, Asan Medical Center, University of Ulsan College of Medicine, Seoul 138‑736, Republic of Korea.
authors.forename: Seol Hwa
authors.initials: SH
authors.lastname: Shin
authors.affiliation: Institute for Innovative Cancer Research, Asan Medical Center, University of Ulsan College of Medicine, Seoul 138‑736, Republic of Korea.
authors.forename: Eun Jin
authors.initials: EJ
authors.lastname: Ju
authors.affiliation: Institute for Innovative Cancer Research, Asan Medical Center, University of Ulsan College of Medicine, Seoul 138‑736, Republic of Korea.
authors.forename: Jinhyang
authors.initials: J
authors.lastname: Choi
authors.affiliation: Institute for Innovative Cancer Research, Asan Medical Center, University of Ulsan College of Medicine, Seoul 138‑736, Republic of Korea.
authors.forename: Jaesook
authors.initials: J
authors.lastname: Park
authors.affiliation: Institute for Innovative Cancer Research, Asan Medical Center, University of Ulsan College of Medicine, Seoul 138‑736, Republic of Korea.
authors.forename: Jae Hee
authors.initials: JH
authors.lastname: Lee
authors.affiliation: Asan Institute for Life Sciences, Asan Medical Center, University of Ulsan College of Medicine, Seoul 138‑736, Republic of Korea.
authors.forename: Inki
authors.initials: I
authors.lastname: Kim
authors.affiliation: Institute for Innovative Cancer Research, Asan Medical Center, University of Ulsan College of Medicine, Seoul 138‑736, Republic of Korea.
authors.forename: Young-Ah
authors.initials: YA
authors.lastname: Suh
authors.affiliation: Institute for Innovative Cancer Research, Asan Medical Center, University of Ulsan College of Medicine, Seoul 138‑736, Republic of Korea.
authors.forename: Jung Jin
authors.initials: JJ
authors.lastname: Hwang
authors.affiliation: Department of Bioengineering Sciences, Graduate School of Bioagricultural Sciences Nagoya University, Aichi 464‑8601, Japan.
authors.forename: Shun'ichi
authors.initials: S
authors.lastname: Kuroda
authors.affiliation: Institute for Innovative Cancer Research, Asan Medical Center, University of Ulsan College of Medicine, Seoul 138‑736, Republic of Korea.
authors.forename: Jung Shin
authors.initials: JS
authors.lastname: Lee
authors.affiliation: Institute for Innovative Cancer Research, Asan Medical Center, University of Ulsan College of Medicine, Seoul 138‑736, Republic of Korea.
authors.forename: Si Yeol
authors.initials: SY
authors.lastname: Song
authors.affiliation: Institute for Innovative Cancer Research, Asan Medical Center, University of Ulsan College of Medicine, Seoul 138‑736, Republic of Korea.
authors.forename: Eun Kyung
authors.initials: EK
authors.lastname: Choi
mesh_terms: D000818:Animals; D002289:Carcinoma, Non-Small-Cell Lung / Q000473:pathology / Q000628:therapy*; D059248:Chemoradiotherapy / Q000379:methods*; D002945:Cisplatin / Q000008:administration & dosage* / Q000009:adverse effects; D004337:Drug Carriers; D066246:ErbB Receptors / Q000037:antagonists & inhibitors*; D006801:Humans; D007674:Kidney Diseases / Q000139:chemically induced / Q000517:prevention & control; D008081:Liposomes; D008175:Lung Neoplasms / Q000473:pathology / Q000628:therapy*; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D058990:Molecular Targeted Therapy / Q000379:methods; D011832:Radiation Injuries / Q000517:prevention & control; D011838:Radiation-Sensitizing Agents / Q000008:administration & dosage* / Q000009:adverse effects; D016896:Treatment Outcome; D014407:Tumor Cells, Cultured; D023041:Xenograft Model Antitumor Assays
chemical_list: D004337:Drug Carriers; D008081:Liposomes; D011838:Radiation-Sensitizing Agents; D066246:ErbB Receptors; D002945:Cisplatin