Cancer-specific uptake of a liganded protein nanocarrier targeting aggressive CXCR4+ colorectal cancer models

María Virtudes Céspedes, Ugutz Unzueta, Patricia Álamo, Alberto Gallardo, Rita Sala, Isolda Casanova, Miguel Angel Pavón, María Antonia Mangues, Manuel Trías, Antonio López-Pousa, Antonio Villaverde, Esther Vázquez, Ramon Mangues

Research output: Contribution to journalArticleResearchpeer-review

24 Citations (Scopus)


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.

Original languageEnglish
Pages (from-to)1987-1996
Number of pages10
JournalNanomedicine: Nanotechnology, Biology, and Medicine
Issue number7
Publication statusPublished - 1 Oct 2016


  • CXCR4 receptor
  • Colorectal cancer metastasis
  • Drug delivery
  • Liganded protein nanocarrier
  • Target cell internalization
  • Tumor uptake


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