Cisplatin crosslinked pH-sensitive nanoparticles for efficient delivery of doxorubicin.
pH responsive cisplatin prodrug crosslinked polysaccharide-based nanoparticles were developed from succinic acid decorated dextran (Dex-SA) for active loading and triggered intracellular release of doxorubicin (DOX). Nanoparticles with uniform size were formed spontaneously in aqueous medium via electrostatic interaction between anionic Dex-SA and cationic DOX, and subsequently transformed into crosslinked nanoparticles (CL-Nanoparticles) in situ by readily crosslinking the micelles via chelate interactions between the ionic polymeric carrier and the platinum (II) antitumor drug. This strategy eliminated the need of organic solvents and sophisticated processes in the drug loading procedure. The in vitro release studies showed that DOX was released from the CL-Nanoparticles in a controlled and pH-dependent manner. Furthermore, the pharmacokinetics and biodistribution investigations indicated that, as compared to the non-crosslinked nanoparticles (NCL-Nanoparticles) and free DOX, the CL-Nanoparticles significantly prolonged the blood circulation time of drug, decreased accumulation in the normal tissues and enriched drug into the tumors. As a consequence, the DOX-loaded CL-Nanoparticles exhibited enhanced therapeutic efficacy in tumor-bearing mice compared with the NCL-Nanoparticles and free DOX, which were further confirmed by the histological and immunohistochemical analyses. These cisplatin prodrug crosslinked polysaccharide nanoparticles proved to be a promising nanomedicine drug delivery system for tumor-targeted delivery of DOX.
Key Laboratory of Polymer Ecomaterials, Changchun Institute of Applied Chemistry, Chinese Academy of Sciences, Changchun 130022, PR China; University of Chinese Academy of Sciences, Beijing 100049, PR China.
Mingqiang
M
Li
Key Laboratory of Polymer Ecomaterials, Changchun Institute of Applied Chemistry, Chinese Academy of Sciences, Changchun 130022, PR China.
Zhaohui
Z
Tang
Key Laboratory of Polymer Ecomaterials, Changchun Institute of Applied Chemistry, Chinese Academy of Sciences, Changchun 130022, PR China; University of Chinese Academy of Sciences, Beijing 100049, PR China.
Shixian
S
Lv
Key Laboratory of Polymer Ecomaterials, Changchun Institute of Applied Chemistry, Chinese Academy of Sciences, Changchun 130022, PR China.
Wantong
W
Song
Laboratory Animal Center, Jilin University, Changchun 130012, PR China.
Hua
H
Hong
State Key Laboratory of Polymer Physics and Chemistry, Changchun Institute of Applied Chemistry, Chinese Academy of Sciences, Changchun 130022, PR China.
Xiabin
X
Jing
Wake Forest Institute for Regenerative Medicine, Wake Forest School of Medicine, Medical Center Boulevard, Winston-Salem, NC 27157, USA. Electronic address: yzhang@wakehealth.edu.
Yuanyuan
Y
Zhang
Key Laboratory of Polymer Ecomaterials, Changchun Institute of Applied Chemistry, Chinese Academy of Sciences, Changchun 130022, PR China. Electronic address: xschen@ciac.ac.cn.
Xuesi
X
Chen
D000818:Animals; D000903:Antibiotics, Antineoplastic / Q000008:administration & dosage* / Q000493:pharmacokinetics; D002945:Cisplatin / Q000737:chemistry*; D004317:Doxorubicin / Q000008:administration & dosage* / Q000493:pharmacokinetics; D006461:Hemolysis; D006863:Hydrogen-Ion Concentration; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D053758:Nanoparticles
D000903:Antibiotics, Antineoplastic; D004317:Doxorubicin; D002945:Cisplatin
Chemotherapy; Controlled drug release; Crosslinking; Drug delivery; Nanoparticle; Polysaccharide