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.
[1]Changchun Univ Sci & Technol, Sch Chem & Environm Engn, Changchun, Peoples R China.
[2]NE Normal Univ, Sch Life Sci, Natl Engn Lab Druggable Gene & Prot Screening, Changchun 130024, Peoples R China.
[3]Chinese Acad Sci, Changchun Inst Appl Chem, State Key Lab Polymer Phys & Chem, Changchun 130022, Peoples R China.
[4]Jilin Univ, Dept Gen Internal Med, Hosp 1, Changchun 130023, Peoples R China.
(8.0+极速模式)