title: Reversal of multidrug resistance in human lung cancer cells by delivery of 3-octadecylcarbamoylacrylic acid-cisplatin-based liposomes.
abstract: Liposome-based drug delivery system would be an innovative and promising candidate to circumvent multidrug resistance (MDR) of cisplatin (CDDP). However, the reversal efficacy of liposomal CDDP was severely impaired by weak cellular uptake and insufficient intracellular drug release. In this study, 3-octadecylcarbamoylacrylic acid-CDDP nanocomplex (OMI-CDDP-N)-based liposomes (OCP-L) with high cellular uptake and sufficient intracellular drug release were designed to circumvent MDR of lung cancer. OMI-CDDP-N was synthesized through a pH-sensitive monocarboxylato and an O→Pt coordinate bond, which is more efficient than CDDP. Also, OCP-L incorporated with OMI-CDDP-N could induce effective cellular uptake, enhanced nuclear distribution, and optimal cellular uptake kinetics. In particular, OCP-L presented superior effects on enhancing cell apoptosis and in vitro cytotoxicity in CDDP-resistant human lung cancer (A549/CDDP) cells. The mechanisms of MDR reversal in A549/CDDP cells by OCP-L could attribute to organic cation transporter 2 restoration, ATPase copper-transporting beta polypeptide suppression, hypoxia-inducible factor 1 α-subunit depletion, and phosphatidylinositol 3-kinase/Akt pathway inhibition. These results demonstrated that OCP-L may provide an effective delivery of CDDP to resistant cells to circumvent MDR and enhance the therapeutic index of the chemotherapy.
authors.affiliation: Department of Pharmaceutics, College of Pharmacy, Shenyang Pharmaceutical University, Shenyang, Liaoning, People's Republic of China.
authors.forename: Juan
authors.initials: J
authors.lastname: Song
authors.affiliation: Department of Pharmaceutics, College of Pharmacy, Shenyang Pharmaceutical University, Shenyang, Liaoning, People's Republic of China.
authors.forename: Weifang
authors.initials: W
authors.lastname: Ren
authors.affiliation: Department of Pharmaceutics, College of Pharmacy, Shenyang Pharmaceutical University, Shenyang, Liaoning, People's Republic of China.
authors.forename: Tingting
authors.initials: T
authors.lastname: Xu
authors.affiliation: Department of Pharmaceutics, College of Pharmacy, Shenyang Pharmaceutical University, Shenyang, Liaoning, People's Republic of China.
authors.forename: Yi
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: Department of Pharmaceutics, College of Pharmacy, Shenyang Pharmaceutical University, Shenyang, Liaoning, People's Republic of China.
authors.forename: Hongyu
authors.initials: H
authors.lastname: Guo
authors.affiliation: Department of Pharmaceutics, College of Pharmacy, Shenyang Pharmaceutical University, Shenyang, Liaoning, People's Republic of China.
authors.forename: Shanshan
authors.initials: S
authors.lastname: Zhu
authors.affiliation: Department of Pharmaceutics, College of Pharmacy, Shenyang Pharmaceutical University, Shenyang, Liaoning, People's Republic of China.
authors.forename: Li
authors.initials: L
authors.lastname: Yang
mesh_terms: D000179:Acrylates / Q000008:administration & dosage / Q000737:chemistry / Q000494:pharmacology*; D000970:Antineoplastic Agents / Q000008:administration & dosage* / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects; D002219:Carbamates / Q000008:administration & dosage / Q000737:chemistry / Q000494:pharmacology*; D049109:Cell Proliferation / Q000187:drug effects; D002945:Cisplatin / Q000008:administration & dosage* / Q000494:pharmacology*; D016503:Drug Delivery Systems; D018432:Drug Resistance, Multiple / Q000187:drug effects*; D019008:Drug Resistance, Neoplasm / Q000187:drug effects*; D006801:Humans; D008081:Liposomes; D008175:Lung Neoplasms / Q000188:drug therapy* / Q000473:pathology; D014407:Tumor Cells, Cultured
chemical_list: C000618477:3-octadecylcarbamoylacrylic acid; D000179:Acrylates; D000970:Antineoplastic Agents; D002219:Carbamates; D008081:Liposomes; D002945:Cisplatin
keywords: 3-octadecylcarbamoylacrylic acid-cisplatin nanocomplexes; cellular uptake; liposomes; multidrug resistance; therapeutic index