Folate‐conjugated thermo‐responsive micelles for tumor targeting

Abstract Folate‐conjugated and thermo‐responsive poly((N‐isopropylacrylamide)‐co‐ acrylamide‐co‐(octadecyl acrylate)‐co‐(folate‐(polyethylene glycol)‐(acrylic acid))) (P(NIPA‐co‐AAm‐co‐ODA‐co‐FPA)) micelles with mean diameter of about 60 nm and lower critical solution temperature (LCST) of about 39°C were synthesized by free radical random copolymerization. Single‐factor tests of acrylamide and octadecyl acrylate were carried out to modulate micelles' LCST and diameter, respectively. LCST, diameter, and morphology of micelles were determined by UV–vis spectrophotometer, laser particle size analyzer, and transmittance electron microscope (TEM), respectively. Fluorescein was then used as a model drug to investigate the drug loading content of micelles. Micelles with maximum amount of octadecyl acrylate (180 mg) were found to yield drug loading content of 10.48%. Near infrared dye No.10 was chosen as the tracer to monitor micelles in vivo. The targeting behaviors of micelles in folate receptor positive Bel‐7402 tumor bearing nude mice were assessed by a self‐constructed near infrared imaging system. Results showed satisfactory targeting capability of the thermo‐responsive micelles toward Bel‐7402 tumors, and targeting accumulation could last for more than 96 h, enabling P(NIPA‐co‐AAm‐co‐ODA‐co‐FPA) micelles to function as a diagnostic reagent as well as a targeted tumor therapy. © 2012 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 100A:3134–3142, 2012.