期刊
NANOMEDICINE-NANOTECHNOLOGY BIOLOGY AND MEDICINE
卷 12, 期 7, 页码 1987-1996出版社
ELSEVIER
DOI: 10.1016/j.nano.2016.04.003
关键词
Drug delivery; Liganded protein nanocarrier; Target cell internalization; Tumor uptake; CXCR4 receptor; Colorectal cancer metastasis
资金
- Plan Estatal de I+D+I
- Instituto de Salud Carlos III
- MINECO
- FEDER [PI15/00378, PI15/00272, PI12/00327, BFU2010-17450]
- AGAUR [2014SGR-132, 2014PROD-00055]
- MaratoTV3 [416/C/2013]
- La Caixa Foundation
- CIBER-BBN Nanomets Intramural Project
- Miguel Servet contract from ISCIII
- Sara Borrell contract from ISCIII
- Josep Carreras Research Institute
Unliganded drug-nanoconjugates accumulate passively in the tumor whereas liganded nanoconjugates promote drug internalization in tumor cells via endocytosis and increase antitumor efficacy. Whether or not tumor cell internalization associates with enhanced tumor uptake is still under debate. We here compared tumor uptake of T22-GFP-H6, a liganded protein carrier targeting the CXCR4 receptor, and the unliganded GFP-H6 carrier in subcutaneous and metastatic colorectal cancer models. T22-GFP-H6 had a higher tumor uptake in primary tumor and metastatic foci than GFP-H6, with no biodistribution or toxicity on normal tissues. T22-GFP-H6 was detected in target CXCR4(+) tumor cell cytosol whereas GFP-H6 was detected in tumor stroma. SDF1-alpha co-administration switched T22-GFP-H6 internalization from CXCR4(+) tumor epithelial cells to the stroma. Therefore, the incorporation of a targeting ligand promotes selective accumulation of the nanocarrier inside target tumor cellswhile increasing whole tumor uptake in a CXCR4-dependent manner, validating T22-GFP-H6 as a CXCR4-targeted drug carrier. (C) 2016 Elsevier Inc. All rights reserved.
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