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Nanomedicine. 2014 Nov;10(8):1649-59. doi: 10.1016/j.nano.2014.05.011. Epub 2014 Jun 4.

Transferrin targeted core-shell nanomedicine for combinatorial delivery of doxorubicin and sorafenib against hepatocellular carcinoma.

Author information

1
Amrita center for Nanosciences and Molecular Medicine, Amrita Institute of Medical Sciences and Research Centre, Amrita Vishwa Vidyapeetham (Amrita University), Kochi, India.
2
Amrita center for Nanosciences and Molecular Medicine, Amrita Institute of Medical Sciences and Research Centre, Amrita Vishwa Vidyapeetham (Amrita University), Kochi, India. Electronic address: shantinair@aims.amrita.edu.
3
Amrita center for Nanosciences and Molecular Medicine, Amrita Institute of Medical Sciences and Research Centre, Amrita Vishwa Vidyapeetham (Amrita University), Kochi, India. Electronic address: manzoork@aims.amrita.edu.

Abstract

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.

KEYWORDS:

Core-shell nanomedicine; Doxorubicin; Hepatocellular carcinoma; Poly(vinyl alcohol); Sorafenib; Transferrin

PMID:
24905399
DOI:
10.1016/j.nano.2014.05.011
[Indexed for MEDLINE]

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