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J Control Release. 2015 Feb 28;200:188-200. doi: 10.1016/j.jconrel.2014.12.039. Epub 2014 Dec 30.

Tumor-penetrating peptide fused EGFR single-domain antibody enhances cancer drug penetration into 3D multicellular spheroids and facilitates effective gastric cancer therapy.

Author information

1
The Comprehensive Cancer Center of Drum-Tower Hospital, Medical School of Nanjing University & Clinical Cancer Institute of Nanjing University, Nanjing, China.
2
Laboratory of Cellular and Molecular Biology, Jiangsu Province Academy of Chinese Medicine, Nanjing, China; Jiangsu Province Hospital on Integration of Chinese and Western Medicine, Nanjing University of Chinese Medicine, Nanjing, China.
3
State Key Laboratory of Natural Medicines, School of Life Science and Technology, China Pharmaceutical University, Nanjing, China.
4
Division of Molecular Pharmaceutics and Center for Nanotechnology in Drug Delivery, Eshelman School of Pharmacy, University of North Carolina at Chapel Hill, Chapel Hill, USA.
5
Laboratory of Cellular and Molecular Biology, Jiangsu Province Academy of Chinese Medicine, Nanjing, China; Jiangsu Province Hospital on Integration of Chinese and Western Medicine, Nanjing University of Chinese Medicine, Nanjing, China. Electronic address: pcao79@yahoo.com.
6
The Comprehensive Cancer Center of Drum-Tower Hospital, Medical School of Nanjing University & Clinical Cancer Institute of Nanjing University, Nanjing, China. Electronic address: baoruiliu@nju.edu.cn.

Abstract

Human tumors, including gastric cancer, frequently express high levels of epidermal growth factor receptors (EGFRs), which are associated with a poor prognosis. Targeted delivery of anticancer drugs to cancerous tissues shows potential in sparing unaffected tissues. However, it has been a major challenge for drug penetration in solid tumor tissues due to the complicated tumor microenvironment. We have constructed a recombinant protein named anti-EGFR-iRGD consisting of an anti-EGFR VHH (the variable domain from the heavy chain of the antibody) fused to iRGD, a tumor-specific binding peptide with high permeability. Anti-EGFR-iRGD, which targets EGFR and αvβ3, spreads extensively throughout both the multicellular spheroids and the tumor mass. The recombinant protein anti-EGFR-iRGD also exhibited antitumor activity in tumor cell lines, multicellular spheroids, and mice. Moreover, anti-EGFR-iRGD could improve anticancer drugs, such as doxorubicin (DOX), bevacizumab, nanoparticle permeability and efficacy in multicellular spheroids. This study draws attention to the importance of iRGD peptide in the therapeutic approach of anti-EGFR-iRGD. As a consequence, anti-EGFR-iRGD could be a drug candidate for cancer treatment and a useful adjunct of other anticancer drugs.

KEYWORDS:

Anti-EGFR sdAb; Doxorubicin hydrochloride (PubChem CID: 443939); Drug delivery; Drug penetration; Fluorescein isothiocyanate (PubChem CID: 18730); Isopropyl β-D-1-thiogalactopyranoside (PubChem CID: 656894); Multicellular spheroids; Paclitaxel (PubChem CID: 36314); Recombinant protein; iRGD

PMID:
25553823
PMCID:
PMC5008032
DOI:
10.1016/j.jconrel.2014.12.039
[Indexed for MEDLINE]
Free PMC Article

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