Multifunctional Micelles for Cancer Cell Targeting, Distribution Imaging, and Anticancer Drug Delivery


  • C.-K.H. and C.-L.L. contributed equally. The authors thank the National Science Council of the Republic of China, Taiwan for financially supporting this work under Contract Nos. NSC 94-2320-B-007-003 and 95-2314-B-007-002. The help of the staff at the NTOU Institute of Marine Biology with TEM observation is gratefully acknowledged. TTY Biopharm Co. Ltd. (Taiwan) kindly provided the doxorubicin hydrochloride. Supporting Information is available online from Wiley InterScience or from the authors.


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.