title: Cisplatin-alginate conjugate liposomes for targeted delivery to EGFR-positive ovarian cancer cells.
abstract: Systemic side effects and low aqueous solubility have limited the clinical use of cisplatin (CDDP) in ovarian carcinoma and have contributed to failures in developing effective drug delivery systems. In order to develop a novel drug delivery system with enhanced efficacy and minimal adverse effects, we exploited the properties of sodium alginate (SA) to synthesize CDDP-SA conjugate (CS), which is highly soluble and readily incorporated into liposomes (CS-PEG-Lip). Epidermal growth factor receptor (EGFR) is overexpressed in many ovarian cancers, therefore we modified EGF on the liposomes (CS-EGF-Lip) to specifically target EGFR-expressing tumors, thereby increasing the bioavailability and efficacy of CDDP. In vitro experiments confirmed that EGF-Lip selectively recognized EGFR-positive SKOV3 cells and effectively penetrated tumor spheroids. We demonstrated that CS-EGF-Lip possessed satisfactory size distribution and exhibited significantly improved encapsulation and loading efficiency. Furthermore, CS-EGF-Lip sustained release of CDDP in vitro, suggesting that CS-EGF-Lip may retain the antitumor activity of CDDP. Inhibition of proliferation and migration was also greater with CS-EGF-Lip compared to CDDP. In vivo xenograft experiments revealed that administration of CS-EGF-Lip enhanced delivery of CDDP into ovarian tumor tissues and improved the antitumor efficacy of CDDP, while reducing nephrotoxicity and body weight loss in mice. These results suggest that CS-EGF-Lip may offer a promising strategy for CDDP delivery in the treatment of EGFR-positive ovarian carcinoma or similar tumors, with enhanced efficacy and fewer adverse effects.
authors.affiliation: Department of Obstetrics and Gynecology, Ren Ji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai 200127, PR China; Shanghai Key Laboratory of Gynecologic Oncology, Shanghai 200127, PR China; State Key Laboratory of Oncogenes and Related Genes, Shanghai Cancer Institute, Ren Ji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai 200032, PR China; Shanghai Health Bureau Key Disciplines and Specialties Foundation, Shanghai 200127, PR China; Key Discipline Project of Ren Ji Hospital, Ren Ji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai 200127, PR China.
authors.forename: Yunfei
authors.initials: Y
authors.lastname: Wang
authors.affiliation: Department of Obstetrics and Gynecology, Ren Ji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai 200127, PR China; Shanghai Key Laboratory of Gynecologic Oncology, Shanghai 200127, PR China; Key Discipline Project of Ren Ji Hospital, Ren Ji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai 200127, PR China.
authors.forename: Jinhua
authors.initials: J
authors.lastname: Zhou
authors.affiliation: Department of Obstetrics and Gynecology, Ren Ji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai 200127, PR China; Shanghai Key Laboratory of Gynecologic Oncology, Shanghai 200127, PR China; State Key Laboratory of Oncogenes and Related Genes, Shanghai Cancer Institute, Ren Ji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai 200032, PR China; Key Discipline Project of Ren Ji Hospital, Ren Ji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai 200127, PR China.
authors.forename: Lihua
authors.initials: L
authors.lastname: Qiu
authors.affiliation: Department of Obstetrics and Gynecology, Ren Ji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai 200127, PR China; Shanghai Key Laboratory of Gynecologic Oncology, Shanghai 200127, PR China.
authors.forename: Xinran
authors.initials: X
authors.lastname: Wang
authors.affiliation: Department of Obstetrics and Gynecology, Ren Ji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai 200127, PR China; Shanghai Key Laboratory of Gynecologic Oncology, Shanghai 200127, PR China.
authors.forename: Lilan
authors.initials: L
authors.lastname: Chen
authors.affiliation: Department of Obstetrics and Gynecology, Ren Ji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai 200127, PR China; Shanghai Key Laboratory of Gynecologic Oncology, Shanghai 200127, PR China; Shanghai Health Bureau Key Disciplines and Specialties Foundation, Shanghai 200127, PR China; Key Discipline Project of Ren Ji Hospital, Ren Ji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai 200127, PR China.
authors.forename: Ting
authors.initials: T
authors.lastname: Liu
authors.affiliation: Department of Obstetrics and Gynecology, Ren Ji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai 200127, PR China; Shanghai Key Laboratory of Gynecologic Oncology, Shanghai 200127, PR China; State Key Laboratory of Oncogenes and Related Genes, Shanghai Cancer Institute, Ren Ji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai 200032, PR China; Shanghai Health Bureau Key Disciplines and Specialties Foundation, Shanghai 200127, PR China; Key Discipline Project of Ren Ji Hospital, Ren Ji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai 200127, PR China. Electronic address: diwen163@163.com.
authors.forename: Wen
authors.initials: W
authors.lastname: Di
mesh_terms: D000464:Alginates / Q000737:chemistry*; D000818:Animals; D000970:Antineoplastic Agents / Q000737:chemistry / Q000494:pharmacology / Q000627:therapeutic use; D017209:Apoptosis / Q000187:drug effects; D002453:Cell Cycle / Q000187:drug effects; D016923:Cell Death / Q000187:drug effects; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D002945:Cisplatin / Q000008:administration & dosage / Q000737:chemistry / Q000494:pharmacology / Q000627:therapeutic use*; D003692:Delayed-Action Preparations; D016503:Drug Delivery Systems; D004705:Endocytosis / Q000187:drug effects; D004815:Epidermal Growth Factor / Q000378:metabolism; D066246:ErbB Receptors / Q000378:metabolism*; D005260:Female; D020723:Glucuronic Acid / Q000737:chemistry; D006603:Hexuronic Acids / Q000737:chemistry; D006801:Humans; D007700:Kinetics; D008081:Liposomes / Q000737:chemistry / Q000648:ultrastructure; D051379:Mice; D008819:Mice, Nude; D053758:Nanoparticles / Q000648:ultrastructure; D010051:Ovarian Neoplasms / Q000188:drug therapy* / Q000473:pathology*; D011092:Polyethylene Glycols / Q000737:chemistry; D012235:Rhodamines / Q000378:metabolism; D018874:Spheroids, Cellular / Q000187:drug effects / Q000378:metabolism
chemical_list: D000464:Alginates; D000970:Antineoplastic Agents; D003692:Delayed-Action Preparations; D006603:Hexuronic Acids; D008081:Liposomes; D012235:Rhodamines; D011092:Polyethylene Glycols; D004815:Epidermal Growth Factor; D020723:Glucuronic Acid; D066246:ErbB Receptors; C029773:rhodamine B; D002945:Cisplatin
keywords: Cisplatin; Epidermal growth factor; Liposome; Ovarian cancer; Sodium alginate; Specific drug delivery