title: Nanoparticle-mediated delivery of multinuclear platinum(IV) prodrugs with enhanced drug uptake and the activity of overcoming drug resistance.
abstract: Here, a nanoparticle-mediated delivery of multinuclear platinum(IV) prodrugs [biodegradable polymer-di-cisPt(IV)] for overcoming cisplatin drug resistance is reported. From the MTT assays, lower IC50 values of polymer-di-cisPt(IV) on A2780DDP cells than A2780 were observed with the lowest resistance factor of 0.7. Inductively coupled plasma mass spectroscopy results showed that more drugs were delivered into cancer cells and greater number of Pt-DNA adducts were formed with the use of the polymer-di-cisPt(IV) conjugate nanoparticles. By a mechanistic study with endocytosis inhibitors to treat A2780 cells, we proved that polymer-di-cisPt(IV) conjugate nanoparticles were internalized by the cancer cells through endocytosis rather than through passive diffusion or copper transporter 1-mediated active transportation. This well illustrates the way how the polymer-di-cisPt(IV) micelles overcome cisplatin resistance.
authors.affiliation: aSchool of Chemistry & Environmental Engineering, Changchun University of Science & Technology bNational Engineering Laboratory for Druggable Gene and Protein Screening, School of Life Science, Northeast Normal University cState Key Laboratory of Polymer Physics and Chemistry, Changchun Institute of Applied Chemistry, Chinese Academy of Sciences dDepartment of General Internal Medicine, The First Hospital of Jilin University, Changchun, China.
authors.forename: Ying
authors.initials: Y
authors.lastname: Gao
authors.forename: Mo
authors.initials: M
authors.lastname: Jiang
authors.forename: Yuqin
authors.initials: Y
authors.lastname: Ma
authors.forename: Shuang
authors.initials: S
authors.lastname: Wu
authors.forename: Wenliang
authors.initials: W
authors.lastname: Li
authors.forename: Xiaoguang
authors.initials: X
authors.lastname: Yang
authors.forename: Yuxin
authors.initials: Y
authors.lastname: Li
authors.forename: Xiabin
authors.initials: X
authors.lastname: Jing
authors.forename: Hongyu
authors.initials: H
authors.lastname: Jiang
mesh_terms: D000970:Antineoplastic Agents / Q000008:administration & dosage* / Q000737:chemistry / Q000378:metabolism; D045744:Cell Line, Tumor; D002945:Cisplatin / Q000008:administration & dosage* / Q000031:analogs & derivatives* / Q000737:chemistry / Q000378:metabolism; D004337:Drug Carriers; D019008:Drug Resistance, Neoplasm; D004354:Drug Screening Assays, Antitumor; D006801:Humans; D008823:Micelles; D053758:Nanoparticles; D011091:Polyesters / Q000737:chemistry; D011107:Polylysine / Q000737:chemistry; D011355:Prodrugs / Q000008:administration & dosage* / Q000737:chemistry / Q000378:metabolism
chemical_list: D000970:Antineoplastic Agents; D004337:Drug Carriers; D008823:Micelles; D011091:Polyesters; D011355:Prodrugs; C572240:methoxy poly(ethylene glycol)-b-poly(epsilon-caprolactone)-b-poly(L-lysine); D011107:Polylysine; D002945:Cisplatin