TY - JOUR
T1 - Cancer-specific uptake of a liganded protein nanocarrier targeting aggressive CXCR4+ colorectal cancer models
AU - Céspedes, María Virtudes
AU - Unzueta, Ugutz
AU - Álamo, Patricia
AU - Gallardo, Alberto
AU - Sala, Rita
AU - Casanova, Isolda
AU - Pavón, Miguel Angel
AU - Mangues, María Antonia
AU - Trías, Manuel
AU - López-Pousa, Antonio
AU - Villaverde, Antonio
AU - Vázquez, Esther
AU - Mangues, Ramon
PY - 2016/10/1
Y1 - 2016/10/1
N2 - © 2016 Elsevier Inc. 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-α 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 cells while increasing whole tumor uptake in a CXCR4-dependent manner, validating T22-GFP-H6 as a CXCR4-targeted drug carrier.
AB - © 2016 Elsevier Inc. 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-α 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 cells while increasing whole tumor uptake in a CXCR4-dependent manner, validating T22-GFP-H6 as a CXCR4-targeted drug carrier.
KW - CXCR4 receptor
KW - Colorectal cancer metastasis
KW - Drug delivery
KW - Liganded protein nanocarrier
KW - Target cell internalization
KW - Tumor uptake
UR - https://ddd.uab.cat/record/174144
U2 - https://doi.org/10.1016/j.nano.2016.04.003
DO - https://doi.org/10.1016/j.nano.2016.04.003
M3 - Article
VL - 12
SP - 1987
EP - 1996
ER -