title: Turning Ineffective Transplatin into a Highly Potent Anticancer Drug via a Prodrug Strategy for Drug Delivery and Inhibiting Cisplatin Drug Resistance.
abstract: Clinically ineffective transplatin is highly potent against cancer cells when transformed into a transplatin(IV) prodrug nanoparticle. Herein, a hydrophobic transplatin(IV) was synthesized by H2O2-oxidization of transplatin and attachment of two hydrophobic aliphatic chains. Transplatin(IV) was subsequently encapsulated by a biodegradable amphiphilic copolymer, MPEG-PLA, forming a well-defined spherical micelles (M(TransPt)). Transplatin(IV) was protected efficiently and could be released under a simulated cancerous intracellular condition. Compared to the cisplatin and transplatin, M(TransPt) showed the highest Pt uptake and a clathrin-dependent endocytosis pathway. Most importantly, M(TransPt) displayed a nanomolar IC50 on A2780 cells and a great potency on cisplatin resistant A2780DDP cell line. Overall, this nanoplatform for delivering trans-geometry platinum(IV) drug exhibits excellent characteristics for enhancing efficacy and overcoming cisplatin drug resistance, and holds a strong promise for clinical use in the near future.
authors.affiliation: National Engineering Laboratory for Druggable Gene and Protein Screening, School of Life Science, Northeast Normal University , Changchun 130024, People's Republic of China.
authors.forename: Wenliang
authors.initials: W
authors.lastname: Li
authors.affiliation: National Engineering Laboratory for Druggable Gene and Protein Screening, School of Life Science, Northeast Normal University , Changchun 130024, People's Republic of China.
authors.forename: Mo
authors.initials: M
authors.lastname: Jiang
authors.affiliation: National Engineering Laboratory for Druggable Gene and Protein Screening, School of Life Science, Northeast Normal University , Changchun 130024, People's Republic of China.
authors.forename: Yue
authors.initials: Y
authors.lastname: Cao
authors.affiliation: Department of Bioengineering, University of Pennsylvania , 210 South 33rd Street, Philadelphia, Pennsylvania 19104-6321, United States.
authors.forename: Lesan
authors.initials: L
authors.lastname: Yan
authors.affiliation: State Key Laboratory of Polymer Physics and Chemistry, Changchun Institute of Applied Chemistry, Chinese Academy of Sciences , Changchun 130022, People's Republic of China.
authors.forename: Ruogu
authors.initials: R
authors.lastname: Qi
authors.affiliation: National Engineering Laboratory for Druggable Gene and Protein Screening, School of Life Science, Northeast Normal University , Changchun 130024, People's Republic of China.
authors.forename: Yuxin
authors.initials: Y
authors.lastname: Li
authors.affiliation: State Key Laboratory of Polymer Physics and Chemistry, Changchun Institute of Applied Chemistry, Chinese Academy of Sciences , Changchun 130022, People's Republic of China.
authors.forename: Xiabin
authors.initials: X
authors.lastname: Jing
mesh_terms: D000970:Antineoplastic Agents / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology; D045744:Cell Line, Tumor; D002945:Cisplatin / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology*; D004337:Drug Carriers / Q000737:chemistry*; D019008:Drug Resistance, Neoplasm / Q000187:drug effects*; D004705:Endocytosis; D006801:Humans; D057927:Hydrophobic and Hydrophilic Interactions; D008823:Micelles; D011091:Polyesters / Q000737:chemistry; D011092:Polyethylene Glycols / Q000737:chemistry; D011355:Prodrugs / Q000378:metabolism*
chemical_list: D000970:Antineoplastic Agents; D004337:Drug Carriers; D008823:Micelles; D011091:Polyesters; D011355:Prodrugs; C034697:transplatin; D011092:Polyethylene Glycols; C033616:poly(lactide); D002945:Cisplatin