Sensitizing nanoparticle based platinum(IV) drugs by curcumin for better chemotherapy.
A polymer-cisplatin(IV) conjugate was prepared by attaching Pt(IV)-COOH to a biodegradable amphiphilic block copolymer containing pendant OH groups. The conjugate can assemble into micelles (M(Pt)) with a mean diameter of ca. 169nm. Further, curcumin (CM) was used to sensitize platinum drug based nanoparticles to overcome cisplatin resistance and enhance antitumor efficacy. In vitro studies showed that M(Pt)/CM combinations had great synergistic effect both on cisplatin sensitive and cisplatin resistant cell lines (A2780 and A2780DDP). In vivo studies showed that M(Pt)/CM had a much lower systemic toxicity and an enhanced antitumor efficacy compared to cisplatin alone or the corresponding cisplatin/CM combinations. Therefore, polymer-cisplatin(IV) conjugate with small molecules that serve as a non-cytotoxic or minimally cytotoxic sensitizer or enhancer provide a promising strategy, which may have potential clinical implications in the near future.
Department of Obstetrics and Gynecology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, China.
Xiang
X
Kang
Department of Medicine, Mount Sinai Roosevelt, 1000 Tenth Avenue, Suite 3A-02, New York, NY 10019, United States.
Chen
C
Zhao
State Key Laboratory of Polymer Physics and Chemistry, Changchun Institute of Applied Chemistry, Chinese Academy of Sciences, Changchun 130022, China; The University of Chinese Academy of Sciences, Beijing 100049, China. Electronic address: lesanyan@gmail.com.
Lesan
L
Yan
State Key Laboratory of Polymer Physics and Chemistry, Changchun Institute of Applied Chemistry, Chinese Academy of Sciences, Changchun 130022, China; The University of Chinese Academy of Sciences, Beijing 100049, China. Electronic address: Ruoguqix@gmail.com.
Ruogu
R
Qi
State Key Laboratory of Polymer Physics and Chemistry, Changchun Institute of Applied Chemistry, Chinese Academy of Sciences, Changchun 130022, China.
Xiabin
X
Jing
Department of Obstetrics and Gynecology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, China.
Zehua
Z
Wang
D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D002945:Cisplatin / Q000737:chemistry / Q000494:pharmacology; D003474:Curcumin / Q000737:chemistry*; D019008:Drug Resistance, Neoplasm; D006801:Humans; D053758:Nanoparticles / Q000737:chemistry*; D010984:Platinum / Q000737:chemistry*
D010984:Platinum; D003474:Curcumin; D002945:Cisplatin
Cisplatin; Combination therapy; Curcumin; Drug delivery; Drug resistance