Amphiphilic oligomer-based micelles as cisplatin nanocarriers for cancer therapy.
Polymeric micelles (∼10 nm) have been prepared from the amphiphilic oligomer comprising oligomeric polystyrene as the hydrophobic inner core and half of EDTA (-N(CH₂COOH)₂) as the hydrophilic outermost shell. After chelating cisplatin with -N(CH₂COOH)₂ in water, polymeric micelles containing Pt on the spherical surface have been easily obtained. Since the chelate group is introduced into the amphiphilic oligomer as the terminal group by a RAFT agent, the chelation of cisplatin with PS(COOH)₂ is almost stoichiometric. The drug carrier based on PS(COOH)₂ showed a high loading efficiency (>70%) towards cisplatin. The release of the therapeutic Pt from the cisplatin-loaded composites (PS(COOH)₂-Pt) triggered under weak acidic conditions resulted in good Pt-release and accumulation in tumor cells. Both in vitro and in vivo, the chelated cisplatin inhibited Sk-Br3 cancer more effectively than the intact cisplatin does. Furthermore, neither PS(COOH)₂ nor PS(COOH)₂-Pt showed obvious systematic toxicity.
Jiangsu Key Laboratory of Advanced Functional Polymer Design and Application, College of Chemistry, Chemical Engineering and Materials Science, Soochow University, Suzhou, Jiangsu 215123, China. lujm@suda.edu.cn linajun@suda.edu.cn.
Xiuxiu
X
Qi
Najun
N
Li
Hongwei
H
Gu
Yujie
Y
Xu
Ying
Y
Xu
Yang
Y
Jiao
Qingfeng
Q
Xu
Hua
H
Li
Jianmei
J
Lu
D000818:Animals; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D002945:Cisplatin / Q000008:administration & dosage* / Q000737:chemistry / Q000633:toxicity; D056831:Coordination Complexes / Q000737:chemistry / Q000633:toxicity; D004337:Drug Carriers / Q000737:chemistry*; D004492:Edetic Acid / Q000737:chemistry; D005260:Female; D006801:Humans; D006863:Hydrogen-Ion Concentration; D057927:Hydrophobic and Hydrophilic Interactions; D051379:Mice; D008819:Mice, Nude; D008823:Micelles; D053758:Nanoparticles / Q000737:chemistry*; D009369:Neoplasms / Q000188:drug therapy* / Q000473:pathology; D011137:Polystyrenes / Q000737:chemistry; D014183:Transplantation, Heterologous
D056831:Coordination Complexes; D004337:Drug Carriers; D008823:Micelles; D011137:Polystyrenes; D004492:Edetic Acid; D002945:Cisplatin