Transferrin Targeted Core-shell Nanomedicine for Combinatorial Delivery of Doxorubicin and Sorafenib Against Hepatocellular Carcinoma
Publication Type:Journal Article
Source:Nanomedicine: Nanotechnology, Biology, and Medicine, Elsevier Inc., Volume 10, Number 8, p.1649-1659 (2014)
Keywords:albumin, antineoplastic activity, article, controlled study, Core-shell, doxorubicin, drug cytotoxicity, drug delivery system, drug efficacy, drug penetration, drug potentiation, drug release, drug targeting, Hepatocellular carcinoma, HepG2 cell line, human, human cell, liver cell carcinoma, molecularly targeted therapy, nanocapsule, nanoencapsulation, nanomedicine, nanoparticle, polyvinyl alcohol, sorafenib, Transferrin, tumor spheroid
Combinatorial drug delivery is an attractive, but challenging requirement of next generation cancer nanomedicines. Here, we report a transferrin-targeted core-shell nanomedicine formed by encapsulating two clinically used single-agent drugs, doxorubicin and sorafenib against liver cancer. Doxorubicin was loaded in poly(vinyl alcohol) nano-core and sorafenib in albumin nano-shell, both formed by a sequential freeze-thaw/coacervation method. While sorafenib from the nano-shell inhibited aberrant oncogenic signaling involved in cell proliferation, doxorubicin from the nano-core evoked DNA intercalation thereby killing >. 75% of cancer cells. Upon targeting using transferrin ligands, the nanoparticles showed enhanced cellular uptake and synergistic cytotoxicity in . 92% of cells, particularly in iron-deficient microenvironment. Studies using 3D spheroids of liver tumor indicated efficient penetration of targeted core-shell nanoparticles throughout the tissue causing uniform cell killing. Thus, we show that rationally designed core-shell nanoparticles can effectively combine clinically relevant single-agent drugs for exerting synergistic activity against liver cancer. From the Clinical Editor: Transferrin-targeted core-shell nanomedicine encapsulating doxorubicin and sorafenib was studied as a drug delivery system against hepatocellular carcinoma, resulting in enhanced and synergistic therapeutic effects, paving the way towards potential future clinical applications of similar techniques. © 2014 Elsevier Inc.
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Cite this Research Publication
G. L. Malarvizhi, Retnakumari, A. P., Nair, S., and Dr. Manzoor K., “Transferrin Targeted Core-shell Nanomedicine for Combinatorial Delivery of Doxorubicin and Sorafenib Against Hepatocellular Carcinoma”, Nanomedicine: Nanotechnology, Biology, and Medicine, vol. 10, pp. 1649-1659, 2014.