Cancer-specific uptake of a liganded protein nanocarrier targeting aggressive CXCR4(+) colorectal cancer models
Por:
Cespedes, MV, Unzueta, U, Alamo, P, Gallardo, A, Sala, R, Casanova, I, Pavon, MA, Mangues, MA, Trias, M, Lopez-Pousa, A, Villaverde, A, Vaazquez, E, Mangues, R
Publicada:
1 oct 2016
Resumen:
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.
Filiaciones:
Cespedes, MV:
Inst Invest Biomed St Pau, Barcelona, Spain
Hosp Santa Creu & Sant Pau, Josep Carreras Res Inst, Barcelona, Spain
CIBER Bioingn Biomat & Nanomed CIBER BBN, Barcelona, Spain
Unzueta, U:
Inst Invest Biomed St Pau, Barcelona, Spain
Hosp Santa Creu & Sant Pau, Josep Carreras Res Inst, Barcelona, Spain
CIBER Bioingn Biomat & Nanomed CIBER BBN, Barcelona, Spain
Alamo, P:
Inst Invest Biomed St Pau, Barcelona, Spain
Hosp Santa Creu & Sant Pau, Josep Carreras Res Inst, Barcelona, Spain
CIBER Bioingn Biomat & Nanomed CIBER BBN, Barcelona, Spain
Gallardo, A:
Inst Invest Biomed St Pau, Barcelona, Spain
Hosp Santa Creu & Sant Pau, Josep Carreras Res Inst, Barcelona, Spain
CIBER Bioingn Biomat & Nanomed CIBER BBN, Barcelona, Spain
Clin Girona, Dept Pathol, Girona, Spain
Sala, R:
Inst Invest Biomed St Pau, Barcelona, Spain
Hosp Santa Creu & Sant Pau, Josep Carreras Res Inst, Barcelona, Spain
CIBER Bioingn Biomat & Nanomed CIBER BBN, Barcelona, Spain
Casanova, I:
Inst Invest Biomed St Pau, Barcelona, Spain
Hosp Santa Creu & Sant Pau, Josep Carreras Res Inst, Barcelona, Spain
CIBER Bioingn Biomat & Nanomed CIBER BBN, Barcelona, Spain
Pavon, MA:
Inst Invest Biomed St Pau, Barcelona, Spain
Hosp Santa Creu & Sant Pau, Josep Carreras Res Inst, Barcelona, Spain
CIBER Bioingn Biomat & Nanomed CIBER BBN, Barcelona, Spain
Mangues, MA:
Inst Invest Biomed St Pau, Barcelona, Spain
Hosp Santa Creu & Sant Pau, Josep Carreras Res Inst, Barcelona, Spain
CIBER Bioingn Biomat & Nanomed CIBER BBN, Barcelona, Spain
Hosp Santa Creu & Sant Pau, Dept Pharm, Barcelona, Spain
Trias, M:
Inst Invest Biomed St Pau, Barcelona, Spain
Hosp Santa Creu & Sant Pau, Josep Carreras Res Inst, Barcelona, Spain
CIBER Bioingn Biomat & Nanomed CIBER BBN, Barcelona, Spain
Hosp Santa Creu & Sant Pau, Dept Gen & Digest Surg, Barcelona, Spain
Lopez-Pousa, A:
Inst Invest Biomed St Pau, Barcelona, Spain
Hosp Santa Creu & Sant Pau, Josep Carreras Res Inst, Barcelona, Spain
CIBER Bioingn Biomat & Nanomed CIBER BBN, Barcelona, Spain
Hosp Santa Creu & Sant Pau, Med Oncol, Barcelona, Spain
Villaverde, A:
CIBER Bioingn Biomat & Nanomed CIBER BBN, Barcelona, Spain
Univ Autonoma Barcelona, Inst Biotecnol & Biomed, Barcelona, Spain
Univ Autonoma Barcelona, Dept Genet & Microbiol, Barcelona, Spain
Vaazquez, E:
CIBER Bioingn Biomat & Nanomed CIBER BBN, Barcelona, Spain
Univ Autonoma Barcelona, Inst Biotecnol & Biomed, Barcelona, Spain
Univ Autonoma Barcelona, Dept Genet & Microbiol, Barcelona, Spain
Mangues, R:
Inst Invest Biomed St Pau, Barcelona, Spain
Hosp Santa Creu & Sant Pau, Josep Carreras Res Inst, Barcelona, Spain
CIBER Bioingn Biomat & Nanomed CIBER BBN, Barcelona, Spain
Green Published
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