Folate-conjugated thermo-responsive micelles for tumor targeting.

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.