title: SapC-DOPS nanovesicles as targeted therapy for lung cancer.
abstract: Lung cancer is the deadliest type of cancer for both men and women. In this study, we evaluate the in vitro and in vivo efficacy of a biotherapeutic agent composed of a lysosomal protein (Saposin C, SapC) and a phospholipid (dioleoylphosphatidylserine, DOPS), which can be assembled into nanovesicles (SapC-DOPS) with selective antitumor activity. SapC-DOPS targets phosphatidylserine, an anionic phospholipid preferentially exposed in the surface of cancer cells and tumor-associated vasculature. Because binding of SapC to phosphatidylserine is favored at acidic pHs, and the latter characterizes the milieu of many solid tumors, we tested the effect of pH on the binding capacity of SapC-DOPS to lung tumor cells. Results showed that SapC-DOPS binding to cancer cells was more pronounced at low pH. Viability assays on a panel of human lung tumor cells showed that SapC-DOPS cytotoxicity was positively correlated with cell surface phosphatidylserine levels, whereas mitochondrial membrane potential measurements were consistent with apoptosis-related cell death. Using a fluorescence tracking method in live mice, we show that SapC-DOPS specifically targets human lung cancer xenografts, and that systemic therapy with SapC-DOPS induces tumor apoptosis and significantly inhibits tumor growth. These results suggest that SapC-DOPS nanovesicles are a promising treatment option for lung cancer.
authors: State Key Laboratory of Reproductive Medicine, Central Laboratory of Nanjing First Hospital, Nanjing Medical University, Nanjing, Jiangsu, China.
authors: Shuli
authors: S
authors: Zhao
authors: Division of Hematology/Oncology, Department of Internal Medicine, University of Cincinnati College of Medicine, Cincinnati, Ohio. Division of Human Genetics, Department of Pediatrics, Cincinnati Children's Hospital Medical Center, Cincinnati, Ohio.
authors: Zhengtao
authors: Z
authors: Chu
authors: Division of Hematology/Oncology, Department of Internal Medicine, University of Cincinnati College of Medicine, Cincinnati, Ohio.
authors: Victor M
authors: VM
authors: Blanco
authors: Immunology and Reproductive Biology Laboratory, Medical School and State Key Laboratory of Pharmaceutical Biotechnology, Nanjing University, Nanjing, Jiangsu, China.
authors: Yunzhong
authors: Y
authors: Nie
authors: Immunology and Reproductive Biology Laboratory, Medical School and State Key Laboratory of Pharmaceutical Biotechnology, Nanjing University, Nanjing, Jiangsu, China.
authors: Yayi
authors: Y
authors: Hou
authors: Division of Hematology/Oncology, Department of Internal Medicine, University of Cincinnati College of Medicine, Cincinnati, Ohio. Division of Human Genetics, Department of Pediatrics, Cincinnati Children's Hospital Medical Center, Cincinnati, Ohio. xiaoyang.qi@uc.edu.
authors: Xiaoyang
authors: X
authors: Qi
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology; D016923:Cell Death / Q000187:drug effects; D045744:Cell Line, Tumor; D005260:Female; D006801:Humans; D006863:Hydrogen-Ion Concentration; D008175:Lung Neoplasms / Q000188:drug therapy*; D008819:Mice, Nude; D058990:Molecular Targeted Therapy; D049329:Nanostructures / Q000737:chemistry*; D010718:Phosphatidylserines / Q000737:chemistry*; D049231:Saposins / Q000494:pharmacology / Q000627:therapeutic use*; D053835:Unilamellar Liposomes / Q000737:chemistry*; D023041:Xenograft Model Antitumor Assays
chemical_list: D000970:Antineoplastic Agents; D010718:Phosphatidylserines; D049231:Saposins; D053835:Unilamellar Liposomes; C042511:1,2-dioleoylphosphatidylserine