Co-delivery of daunomycin and oxaliplatin by biodegradable polymers for safer and more efficacious combination therapy.
An oxaliplatin pro-drug (Oxa(IV)-COOH) with an axial carboxyl group was synthesized and conjugated to biodegradable polymers with pendant hydroxyl groups to prepare polymer-Oxa(IV) conjugates. A hydrophobic anthracycline-based drug, daunorubicin (DRB) was conjugated to similar biodegradable polymers with carboxyl groups to synthesize polymer-DRB conjugates. The two drug conjugates have the similar polymer backbone and are amphiphilic; thus, they can co-assemble into composite micelles. In the composite micelles, the polymer-Oxa(IV) conjugates can release clinically widely used water soluble anticancer drug oxaliplatin (Oxa(II)) upon reduction, while polymer-DRB conjugate is thought to release DRB via acid hydrolysis in the cancer cells. In this way, combination of the hydrophilic platinum drug Oxa(II) and hydrophobic drug DRB can be realized by delivering them in one platform. Moreover, the composite micelles showed reduced systematic toxicity and greater synergistic effect than combination of small molecules of the two anticancer drugs both in vitro and in vivo; thus, this polymer based combination therapy can be useful in future clinic application.
State Key Laboratory of Polymer Physics and Chemistry, Changchun Institute of Applied Chemistry, Chinese Academy of Sciences, Changchun 130022, People's Republic of China.
Haihua
H
Xiao
Wenliang
W
Li
Ruogu
R
Qi
Lesan
L
Yan
Rui
R
Wang
Shi
S
Liu
Yonghui
Y
Zheng
Zhigang
Z
Xie
Yubin
Y
Huang
Xiabin
X
Jing
D000970:Antineoplastic Agents / Q000008:administration & dosage; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage*; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D003630:Daunorubicin / Q000008:administration & dosage; D004337:Drug Carriers / Q000008:administration & dosage*; D006801:Humans; D008823:Micelles; D009944:Organoplatinum Compounds / Q000008:administration & dosage; D000077150:Oxaliplatin; D011108:Polymers / Q000008:administration & dosage*; D011355:Prodrugs / Q000008:administration & dosage
D000970:Antineoplastic Agents; D004337:Drug Carriers; D008823:Micelles; D009944:Organoplatinum Compounds; D011108:Polymers; D011355:Prodrugs; D000077150:Oxaliplatin; D003630:Daunorubicin