Highly stable core-surface-crosslinked nanoparticles as cisplatin carriers for cancer chemotherapy.
Cisplatin is a potent anticancer drug with low solubility in water. A new type of highly stable polymer micelles, namely core-surface-crosslinked nanoparticles (SCNPs) made from amphiphilic brush copolymers, were evaluated as the carrier of cisplatin. Cisplatin could be loaded in the SCNPs with poly(epsilon-caprolactone) (PCL) cores and hydrophilic poly(ethylene glycol) (PEG) or poly[2-(N,N-dimethylamino)ethyl methacrylate] (PDMA) shells with high loading efficiency (approximately 90%). In vitro cellular uptake experiments indicated that both SCNPs could be easily taken up by SKOV-3 ovarian cancer cells. Both cell proliferation assay and IC50 measurements indicated that cisplatin encapsulated in the SCNPs had much enhanced cytotoxicity to the cancer cells compared to free cisplatin. The positive charges on the PCL/PDMA SCNPs promoted the cellular internalization of the nanoparticles, resulting in higher cytotoxicity of cisplatin in these SCNPs. The IC50 of the cisplatin encapsulated in PCL/PDMA SCNPs was as low as 0.01 microg/mL, lower than that of cisplatin in PCL/PEG SCNPs and free cisplatin.
Xu
Peisheng
P
Department of Chemical and Petroleum Engineering, University of Wyoming, Laramie, WY 82071-3375, USA.
Van Kirk
Edward A
EA
Li
Shiyan
S
Murdoch
William J
WJ
Ren
Jun
J
Hussain
Muhammad Delwar
MD
Radosz
Maciej
M
Shen
Youqing
Y
D000970:Antineoplastic Agents / Q000633:toxicity*; D002208:Caproates / Q000737:chemistry; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D002945:Cisplatin / Q000633:toxicity*; D003432:Cross-Linking Reagents / Q000737:chemistry*; D004337:Drug Carriers / Q000737:chemistry*; D004355:Drug Stability; D006801:Humans; D020128:Inhibitory Concentration 50; D007783:Lactones / Q000737:chemistry; D008823:Micelles; D018613:Microscopy, Confocal; D008956:Models, Chemical; D008970:Molecular Weight; D049329:Nanostructures / Q000737:chemistry* / Q000648:ultrastructure; D011092:Polyethylene Glycols / Q000737:chemistry; D011108:Polymers / Q000138:chemical synthesis / Q000737:chemistry
D000970:Antineoplastic Agents; D002208:Caproates; D003432:Cross-Linking Reagents; D004337:Drug Carriers; D007783:Lactones; D008823:Micelles; D011108:Polymers; D011092:Polyethylene Glycols; C121056:caprolactone; D002945:Cisplatin