Cyclic RGD-conjugated Pluronic® blending system for active, targeted drug delivery

Chaemin Lim,1,* Junseong Moon,1,* Taehoon Sim,1 Ngoc Ha Hoang,1 Woong Roeck Won,1 Eun Seong Lee,2 Yu Seok Youn,3 Han-Gon Choi,4 Kyungsoo Oh,1 Kyung Taek Oh1 1College of Pharmacy, Chung-Ang University, Seoul, Republic of Korea; 2Division of Biotechnology, The Catholic University of Korea, Bucheon, Republic of Korea; 3School of Pharmacy, SungKyunKwan University, Suwon, Republic of Korea; 4College of Pharmacy, Institute of Pharmaceutical Science and Technology, Hanyang University, Ansan, Republic of Korea *These authors contributed equally to this work Background: Blending micellar systems of different types of polymers has been proposed as an efficient approach for tailor-made drug formulations. The lamellar structure of hydrophobic polymers may provide a high drug loading capacity, and hydrophilic polymers may provide good colloidal stability. Methods: In this study, the anticancer model drug docetaxel was loaded onto a nanosized blending micellar system with two pluronics (L121/F127). To achieve increased antitumor activity, the cyclic arginine-glycine-aspartic acid tripeptide (cRGD) as an active tumor targeting ligand was conjugated to the blending system.Results: The docetaxel-loaded Pluronic blending system exhibited a higher drug loading capacity than that of F127 and showed high colloidal stability with a spherical structure. cRGD conjugates demonstrated enhanced drug cellular uptake and anticancer activity against αvβ3 integrin-overexpressing U87MG cancer cells. In vivo animal imaging also revealed that the prepared cRGD-conjugated nanoparticles effectively accumulated at the targeted tumor site through an active and passive targeting strategy. Conclusion: Accordingly, the prepared nanosized system shows potential as a tailor-made, active targeting, nanomedicinal platform for anticancer therapy. We believe that this novel nanoplatform will provide insights for advancement of tumor therapy. Keywords: blending micellar system, docetaxel, cyclic RGD, Pluronic L121/F127, active targeting, nanomedicine