Degradable cisplatin-releasing core-shell nanogels from zwitterionic poly(beta -aminoester)-graft-PEG for cancer chemotherapy.
Cisplatin conjugated onto macromolecules or loaded in micelles can be preferentially delivered to tumors to minimize its toxicity to healthy tissues and increase its drug efficacy. Herein, we report cisplatin-containing nanogels possibly useful for targeted delivery of cisplatin. Carboxylic acid-functionalized poly(beta -aminoester)graft-poly(ethylene glycol) copolymers were synthesized by cocondensation polymerization of piperazine with 2,2-bis(acryloxymethyl)propionic acid, PEG 2,2-bis(acryloxymethyl)propionate macromonomer (mPEG). The graft copolymers formed 100-200 nm nanogels with low size-distribution by the complexation of their carboxylic groups with cisplatin. The nanogels were negatively charged and had a PEG outer layer. Thus, they had "stealth properties" suitable for in vivo applications. The nanogels had significantly lower in vitro cytotoxicity to SKOV-3 ovarian cancer cells than free cisplatin, but similar anticancer activity toward SKOV-3 tumors xenografted to immunocompromised mice.
Jin
Wei
W
Department of Chemical and Petroleum Engineering, University of Wyoming, Laramie, Wyoming, USA.
Xu
Peisheng
P
Zhan
Yihong
Y
Shen
Youqing
Y
Van Kirk
Edward A
EA
Alexander
Brenda
B
Murdoch
William J
WJ
Liu
Lijian
L
Isaak
Dale D
DD
D000818:Animals; D000970:Antineoplastic Agents / Q000138:chemical synthesis / Q000493:pharmacokinetics / Q000627:therapeutic use; D002264:Carboxylic Acids / Q000737:chemistry; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D002945:Cisplatin / Q000138:chemical synthesis / Q000493:pharmacokinetics / Q000627:therapeutic use*; D004952:Esters / Q000737:chemistry*; D005260:Female; D006801:Humans; D008297:Male; D051379:Mice; D008819:Mice, Nude; D008956:Models, Chemical; D015394:Molecular Structure; D000080385:Nanogels; D010051:Ovarian Neoplasms / Q000188:drug therapy* / Q000473:pathology; D010316:Particle Size; D011092:Polyethylene Glycols / Q000138:chemical synthesis / Q000737:chemistry* / Q000493:pharmacokinetics / Q000627:therapeutic use; D011094:Polyethyleneimine / Q000138:chemical synthesis / Q000493:pharmacokinetics / Q000627:therapeutic use*; D011108:Polymers / Q000737:chemistry*; D012995:Solubility; D013997:Time Factors; D047368:Tumor Burden / Q000187:drug effects; D023041:Xenograft Model Antitumor Assays / Q000379:methods
D000970:Antineoplastic Agents; D002264:Carboxylic Acids; D004952:Esters; D000080385:Nanogels; D011108:Polymers; C507253:poly(beta-amino ester); C413692:polyethylene glycol polyethyleneimine nanogel; D011092:Polyethylene Glycols; D011094:Polyethyleneimine; D002945:Cisplatin