Folate-conjugated PEG-derivatized Embelin as A Versatile Nanocarrier for the Targeted Delivery of Doxorubicin with Reversal of Multidrug Resistance

1,2,3Jianqin Lu, 1,2,3Yixian Huang, 2Wenchen Zhao, 4Hao Liu, 2Robert B Gibbs, 1,2,3Jiang Li, 1,2,3Song Li

1Center for Pharmacogenetics, 2Department of Pharmaceutical Sciences, School of Pharmacy; 3University of Pittsburgh Cancer Institute, University of Pittsburgh, Pittsburgh, PA, 15261, USA;
4Department of Molecular Biosciences, University of Kansas, Lawrence, KS, 66045, USA

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Summary
In this report, targeted delivery of DOX to breast tumors was successfully achieved using folic acid-conjugated PEG-derivatized Embelin (FA-PEG5K-EB2) as a novel and multifunctional nanomicellar carrier. FA-PEG5K-EB2 significantly facilitated the intracellular uptake of DOX over free DOX and PEGylated liposomal DOX (Doxil®) in breast cancer cells, 4T1.2, and drug resistant cells, NCI/ADR-RES. More importantly, DOX/FA-PEG5K-EB2 mixed micelles demonstrated significantly improved tumor growth inhibitory effect with minimal toxicity in comparison to free DOX and Doxil® in breast tumor model.

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