A prodrug strategy to deliver cisplatin(IV) and paclitaxel in nanomicelles to improve efficacy and tolerance.
A strategy of preparing composite micelles containing both cisplatin(IV) prodrug and paclitaxel was developed, i.e., synthesizing a cisplatin(IV) conjugate and a paclitaxel conjugate starting with the same biodegradable and amphiphilic block copolymer, and co-assembling the two conjugates. The composite micelles could release effective anticancer drug cisplatin(II) upon cellular reduction and PTX via acid hydrolysis once they came into the cancerous cells. Moreover, the composite micelles displayed synergistic effect in vitro and the combination therapy in micellar dosage-form led to reduced systematic toxicity and enhanced antitumor efficacy in vivo.
State Key Laboratory of Polymer Physics and Chemistry, Changchun Institute of Applied Chemistry, Chinese Academy of Sciences, Changchun 130022, China.
Haihua
H
Xiao
Haiqin
H
Song
Qiang
Q
Yang
Haidong
H
Cai
Ruogu
R
Qi
Lesan
L
Yan
Shi
S
Liu
Yonghui
Y
Zheng
Yubin
Y
Huang
Tongjun
T
Liu
Xiabin
X
Jing
D000818:Animals; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage / Q000009:adverse effects / Q000494:pharmacology / Q000627:therapeutic use; D016923:Cell Death / Q000187:drug effects; D045744:Cell Line, Tumor; D002945:Cisplatin / Q000008:administration & dosage / Q000009:adverse effects / Q000494:pharmacology / Q000627:therapeutic use*; D016503:Drug Delivery Systems / Q000379:methods*; D006801:Humans; D020128:Inhibitory Concentration 50; D051379:Mice; D008823:Micelles; D053758:Nanoparticles / Q000737:chemistry* / Q000648:ultrastructure; D009369:Neoplasms / Q000188:drug therapy / Q000473:pathology; D017239:Paclitaxel / Q000008:administration & dosage / Q000009:adverse effects / Q000494:pharmacology / Q000627:therapeutic use*; D010316:Particle Size; D011108:Polymers / Q000138:chemical synthesis / Q000737:chemistry; D011355:Prodrugs / Q000008:administration & dosage / Q000009:adverse effects / Q000494:pharmacology / Q000627:therapeutic use*; D055672:Static Electricity; D014018:Tissue Distribution / Q000187:drug effects; D016896:Treatment Outcome
D008823:Micelles; D011108:Polymers; D011355:Prodrugs; D017239:Paclitaxel; D002945:Cisplatin