Folate-modified chitosan micelles with enhanced tumor targeting evaluated by near infrared imaging system

Folate modified chitosan micelles were synthesized for cancer-specific targeting and drug delivery. Receptor-mediated uptake and drug delivery were characterized in vitro and in a small animal model of cancer after loading with hydrophobic fluorescent dyes as drug models. Hydrophilic succinic anhydride and hydrophobic octaldehyde were reacted with chitosan respectively to form amphipathic N-succinyl-N'-octyl chitosan (SO-chitosan). SO-chitosan was covalently modified with folate to form folate-modified N-succinyl-N'-octyl chitosan (folate-SO-chitosan). The folate-SO-chitosan micelles were obtained through self-assembling and maintained a stable core-shell structure with average diameter of about 136nm up to 15 days. The prepared folate-SO-chitosan micelles displayed a good drug loading content (12.17%), entrapment efficiency (69.32%) and sustained release behavior for the model drug fluorescein. The in vitro cellular uptake and in vivo tumor targeting ability of the folate-SO-chitosan micelles were evaluated by fluorescence microscopy and near infrared imaging, respectively. In vitro and in vivo results demonstrated enhanced targeting behaviors in a folate receptor positive tumor model (Bel-7402), which suggests that the folate-SO-chitosan micelles are promising tumor targeting carriers for hydrophobic diagnostic agents as well as anti-tumor agents. (C) 2011 Elsevier Ltd. All rights reserved.