title: Cancer-specific uptake of a liganded protein nanocarrier targeting aggressive CXCR4+colorectal cancer models.
abstract: 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.
authors.affiliation: Institut d'Investigacions Biomèdiques Sant Pau and Josep Carreras Research Institute, Hospital de Sant Pau, and CIBER de Bioingenieria, Biomateriales y Nanomedicina (CIBER-BBN), Barcelona, Spain.
authors.forename: María Virtudes
authors.initials: MV
authors.lastname: Céspedes
authors.affiliation: Institut d'Investigacions Biomèdiques Sant Pau and Josep Carreras Research Institute, Hospital de Sant Pau, and CIBER de Bioingenieria, Biomateriales y Nanomedicina (CIBER-BBN), Barcelona, Spain.
authors.forename: Ugutz
authors.initials: U
authors.lastname: Unzueta
authors.affiliation: Institut d'Investigacions Biomèdiques Sant Pau and Josep Carreras Research Institute, Hospital de Sant Pau, and CIBER de Bioingenieria, Biomateriales y Nanomedicina (CIBER-BBN), Barcelona, Spain.
authors.forename: Patricia
authors.initials: P
authors.lastname: Álamo
authors.affiliation: Institut d'Investigacions Biomèdiques Sant Pau and Josep Carreras Research Institute, Hospital de Sant Pau, and CIBER de Bioingenieria, Biomateriales y Nanomedicina (CIBER-BBN), Barcelona, Spain; Department of Pathology, Clínica Girona, Girona, Spain.
authors.forename: Alberto
authors.initials: A
authors.lastname: Gallardo
authors.affiliation: Institut d'Investigacions Biomèdiques Sant Pau and Josep Carreras Research Institute, Hospital de Sant Pau, and CIBER de Bioingenieria, Biomateriales y Nanomedicina (CIBER-BBN), Barcelona, Spain.
authors.forename: Rita
authors.initials: R
authors.lastname: Sala
authors.affiliation: Institut d'Investigacions Biomèdiques Sant Pau and Josep Carreras Research Institute, Hospital de Sant Pau, and CIBER de Bioingenieria, Biomateriales y Nanomedicina (CIBER-BBN), Barcelona, Spain.
authors.forename: Isolda
authors.initials: I
authors.lastname: Casanova
authors.affiliation: Institut d'Investigacions Biomèdiques Sant Pau and Josep Carreras Research Institute, Hospital de Sant Pau, and CIBER de Bioingenieria, Biomateriales y Nanomedicina (CIBER-BBN), Barcelona, Spain.
authors.forename: Miguel Angel
authors.initials: MA
authors.lastname: Pavón
authors.affiliation: Institut d'Investigacions Biomèdiques Sant Pau and Josep Carreras Research Institute, Hospital de Sant Pau, and CIBER de Bioingenieria, Biomateriales y Nanomedicina (CIBER-BBN), Barcelona, Spain; Department of Pharmacy. Hospital de Sant Pau, Barcelona, Spain.
authors.forename: María Antonia
authors.initials: MA
authors.lastname: Mangues
authors.affiliation: Institut d'Investigacions Biomèdiques Sant Pau and Josep Carreras Research Institute, Hospital de Sant Pau, and CIBER de Bioingenieria, Biomateriales y Nanomedicina (CIBER-BBN), Barcelona, Spain; Department of General and Digestive Surgery. Hospital de Sant Pau, Barcelona, Spain.
authors.forename: Manuel
authors.initials: M
authors.lastname: Trías
authors.affiliation: Institut d'Investigacions Biomèdiques Sant Pau and Josep Carreras Research Institute, Hospital de Sant Pau, and CIBER de Bioingenieria, Biomateriales y Nanomedicina (CIBER-BBN), Barcelona, Spain; Medical Oncology, Hospital de Sant Pau, Barcelona, Spain.
authors.forename: Antonio
authors.initials: A
authors.lastname: López-Pousa
authors.affiliation: CIBER de Bioingeniería, Biomateriales y Nanomedicina (CIBER-BBN), Bellaterra, Barcelona, and Institut de Biotecnologia i de Biomedicina and Departament de Genètica i de Microbiologia, Universitat Autònoma de Barcelona, Bellaterra, Barcelona, Spain.
authors.forename: Antonio
authors.initials: A
authors.lastname: Villaverde
authors.affiliation: CIBER de Bioingeniería, Biomateriales y Nanomedicina (CIBER-BBN), Bellaterra, Barcelona, and Institut de Biotecnologia i de Biomedicina and Departament de Genètica i de Microbiologia, Universitat Autònoma de Barcelona, Bellaterra, Barcelona, Spain. Electronic address: esther.vazquez@uab.es.
authors.forename: Esther
authors.initials: E
authors.lastname: Vázquez
authors.affiliation: Institut d'Investigacions Biomèdiques Sant Pau and Josep Carreras Research Institute, Hospital de Sant Pau, and CIBER de Bioingenieria, Biomateriales y Nanomedicina (CIBER-BBN), Barcelona, Spain. Electronic address: rmangues@santpau.cat.
authors.forename: Ramon
authors.initials: R
authors.lastname: Mangues
mesh_terms: D015179:Colorectal Neoplasms / Q000188:drug therapy*; D004337:Drug Carriers; D004705:Endocytosis; D006801:Humans; D008024:Ligands; D036103:Nanotechnology; D010455:Peptides; D019718:Receptors, CXCR4; D015398:Signal Transduction; D014018:Tissue Distribution
chemical_list: D004337:Drug Carriers; D008024:Ligands; D010455:Peptides; D019718:Receptors, CXCR4; C516580:T22 peptide
keywords: CXCR4 receptor; Colorectal cancer metastasis; Drug delivery; Liganded protein nanocarrier; Target cell internalization; Tumor uptake