Journal
ADVANCED FUNCTIONAL MATERIALS
Volume 17, Issue 14, Pages 2291-2297Publisher
WILEY-V C H VERLAG GMBH
DOI: 10.1002/adfm.200600818
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Multifunctional micelles for cancer cell targeting, distribution imaging, and anticancer drug delivery were prepared from an environmentally-sensitive graft copolymer, poly(N-isopropyl acrylamide-co-methacryl acid)-g-poly(D,L-lactide) (P(NIPAAm-co-MAAc)-g-PLA), a diblock copolymer, methoxy poly(ethylene glycol)-b-Poly(D,L-lactide) (mPEG-PLA) and two functionalized diblock copolymers, galactosamine-PEG-PLA (Gal-PEG-PLA) and fluorescein isothiocyanate-PEG-PLA (FITC-PEG-PLA). Anticancer drug, free base doxorubicin (Dox) was incorporated into the inner core of multifunctional micelles by dialysis. From the drug release study, a change in pH (from pH 7.4 to 5.0) deformed the structure of the inner core from that of aggregated P(NIPAAm-co-MAAc), causing the release of a significant quantity of doxorubicin (Dox) from multifunctional micelles. Multifunctional micelles target specific tumors by an asialoglycoprotein (HepG2 cells)-Gal (multifunctional micelle) receptor-mediated tumor targeting mechanism. This mechanism then causes intracellular pH changes which induce Dox release from multifunctional micelles and that micelles have strong effects on the viability of HepG2 cells and are abolished by galactose. Confocal laser scanning microscopy (CLSM) reveals a clear distribution of multifunctional micelles. With careful design and sophisticated manipulation, polymeric micelles can be widely used in cancer diagnosis, cancer targeting, and cancer therapy simultaneously.
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