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Nanoparticles inhibit cancer cell invasion and enhance antitumor efficiency by targeted drug delivery via cell surface-related GRP78

Authors Zhao L, Li H, Shi Y, Wang G, Liu L, Su C, Su R

Received 24 September 2014

Accepted for publication 9 November 2014

Published 30 December 2014 Volume 2015:10(1) Pages 245—256

DOI https://doi.org/10.2147/IJN.S74868

Checked for plagiarism Yes

Review by Single-blind

Peer reviewer comments 4

Editor who approved publication: Dr Thomas J Webster

Liang Zhao,1,* Hongdan Li,2,* Yijie Shi,1 Guan Wang,2 Liwei Liu,1 Chang Su,3 Rongjian Su2

1School of Pharmacy, Liaoning Medical University, Jinzhou, People’s Republic of China; 2Central Laboratory of Liaoning Medical University, Jinzhou, People’s Republic of China; 3School of Veterinary Medicine, Liaoning Medical University, Jinzhou, People’s Republic of China

*These authors contributed equally to this work

Abstract: Nanoparticles (NPs) which target specific agents could effectively recognize the target cells and increase the stability of chemical agents by encapsulation. As such, NPs have been widely used in cancer treatment research. Recently, over 90% of treatment failure cases in patients with metastatic cancer were attributed to resistance to chemotherapy. Surface-exposed glucose-regulated protein of 78 kDa (GRP78) is expressed highly on many tumor cell surfaces in many human cancers and is related to the regulation of invasion and metastasis. Herein, we report that NPs conjugated with antibody against GRP78 (mAb GRP78-NPs) inhibit the adhesion, invasion, and metastasis of hepatocellular carcinoma (HCC) and promote drug delivery of 5-fluorouracil into GRP78 high-expressed human hepatocellular carcinoma cells. Our new findings suggest that mAb GRP78-NPs could enhance drug accumulation by effectively transporting NPs into cell surface GRP78-overexpressed human hepatocellular carcinoma cells and then inhibit cell proliferation and viability and induce cell apoptosis by regulating caspase-3. In brief, mAb GRP78-NPs effectively inhibit cancer cell invasion and enhance antitumor efficiency by targeted drug delivery.

Keywords: 5-Fu, apoptosis, HCC, caspase-3

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