title: Intracellular targeting of CD44+ cells with self-assembling, protein only nanoparticles.
abstract: CD44 is a multifunctional cell surface protein involved in proliferation and differentiation, angiogenesis and signaling. The expression of CD44 is up-regulated in several types of human tumors and particularly in cancer stem cells, representing an appealing target for drug delivery in the treatment of cancer. We have explored here several protein ligands of CD44 for the construction of self-assembling modular proteins designed to bind and internalize target cells. Among five tested ligands, two of them (A5G27 and FNI/II/V) drive the formation of protein-only, ring-shaped nanoparticles of about 14 nm that efficiently bind and penetrate CD44(+) cells by an endosomal route. The potential of these newly designed nanoparticles is evaluated regarding the need of biocompatible nanostructured materials for drug delivery in CD44-linked conditions.
authors.affiliation: Departament de Genètica i de Microbiologia, Universitat Autònoma de Barcelona, Bellaterra, 08193 Barcelona, Spain; Institut de Biotecnologia i de Biomedicina, Universitat Autònoma de Barcelona, Bellaterra, 08193 Barcelona, Spain; CIBER en Bioingeniería, Biomateriales y Nanomedicina (CIBER-BBN), Zaragoza, Spain.
authors.forename: Mireia
authors.initials: M
authors.lastname: Pesarrodona
authors.affiliation: Departament de Genètica i de Microbiologia, Universitat Autònoma de Barcelona, Bellaterra, 08193 Barcelona, Spain; Institut de Biotecnologia i de Biomedicina, Universitat Autònoma de Barcelona, Bellaterra, 08193 Barcelona, Spain; CIBER en Bioingeniería, Biomateriales y Nanomedicina (CIBER-BBN), Zaragoza, Spain.
authors.forename: Neus
authors.initials: N
authors.lastname: Ferrer-Miralles
authors.affiliation: Departament de Genètica i de Microbiologia, Universitat Autònoma de Barcelona, Bellaterra, 08193 Barcelona, Spain; Institut de Biotecnologia i de Biomedicina, Universitat Autònoma de Barcelona, Bellaterra, 08193 Barcelona, Spain; CIBER en Bioingeniería, Biomateriales y Nanomedicina (CIBER-BBN), Zaragoza, Spain.
authors.forename: Ugutz
authors.initials: U
authors.lastname: Unzueta
authors.affiliation: CIBER en Bioingeniería, Biomateriales y Nanomedicina (CIBER-BBN), Zaragoza, Spain; CIBBIM-Nanomedicine, Hospital Universitari Vall d'Hebron and Vall d'Hebron Institut de Recerca, Universitat Autònoma de Barcelona, 08035 Barcelona, Spain.
authors.forename: Petra
authors.initials: P
authors.lastname: Gener
authors.affiliation: CIBER en Bioingeniería, Biomateriales y Nanomedicina (CIBER-BBN), Zaragoza, Spain; Department of Molecular Nanoscience and Organic Materials, Institut de Ciència de Materials de Barcelona (CSIC), Bellaterra, 08193 Barcelona, Spain.
authors.forename: Witold
authors.initials: W
authors.lastname: Tatkiewicz
authors.affiliation: CIBER en Bioingeniería, Biomateriales y Nanomedicina (CIBER-BBN), Zaragoza, Spain; Department of Molecular Nanoscience and Organic Materials, Institut de Ciència de Materials de Barcelona (CSIC), Bellaterra, 08193 Barcelona, Spain.
authors.forename: Ibane
authors.initials: I
authors.lastname: Abasolo
authors.affiliation: CIBER en Bioingeniería, Biomateriales y Nanomedicina (CIBER-BBN), Zaragoza, Spain; CIBBIM-Nanomedicine, Hospital Universitari Vall d'Hebron and Vall d'Hebron Institut de Recerca, Universitat Autònoma de Barcelona, 08035 Barcelona, Spain.
authors.forename: Imma
authors.initials: I
authors.lastname: Ratera
authors.affiliation: CIBER en Bioingeniería, Biomateriales y Nanomedicina (CIBER-BBN), Zaragoza, Spain; CIBBIM-Nanomedicine, Hospital Universitari Vall d'Hebron and Vall d'Hebron Institut de Recerca, Universitat Autònoma de Barcelona, 08035 Barcelona, Spain.
authors.forename: Jaume
authors.initials: J
authors.lastname: Veciana
authors.affiliation: CIBER en Bioingeniería, Biomateriales y Nanomedicina (CIBER-BBN), Zaragoza, Spain; Department of Molecular Nanoscience and Organic Materials, Institut de Ciència de Materials de Barcelona (CSIC), Bellaterra, 08193 Barcelona, Spain.
authors.forename: Simó
authors.initials: S
authors.lastname: Schwartz
authors.affiliation: Departament de Genètica i de Microbiologia, Universitat Autònoma de Barcelona, Bellaterra, 08193 Barcelona, Spain; Institut de Biotecnologia i de Biomedicina, Universitat Autònoma de Barcelona, Bellaterra, 08193 Barcelona, Spain; CIBER en Bioingeniería, Biomateriales y Nanomedicina (CIBER-BBN), Zaragoza, Spain. Electronic address: antoni.villaverde@uab.cat.
authors.forename: Antonio
authors.initials: A
authors.lastname: Villaverde
authors.affiliation: Departament de Genètica i de Microbiologia, Universitat Autònoma de Barcelona, Bellaterra, 08193 Barcelona, Spain; Institut de Biotecnologia i de Biomedicina, Universitat Autònoma de Barcelona, Bellaterra, 08193 Barcelona, Spain; CIBER en Bioingeniería, Biomateriales y Nanomedicina (CIBER-BBN), Zaragoza, Spain.
authors.forename: Esther
authors.initials: E
authors.lastname: Vazquez
mesh_terms: D045744:Cell Line, Tumor; D004705:Endocytosis; D005353:Fibronectins / Q000737:chemistry; D057809:HEK293 Cells; D006801:Humans; D018960:Hyaluronan Receptors / Q000378:metabolism*; D007797:Laminin / Q000737:chemistry; D008024:Ligands; D053758:Nanoparticles / Q000008:administration & dosage* / Q000737:chemistry; D010455:Peptides / Q000008:administration & dosage / Q000737:chemistry*
chemical_list: D005353:Fibronectins; D018960:Hyaluronan Receptors; D007797:Laminin; D008024:Ligands; D010455:Peptides
keywords: Biomaterials; CD44; Drug delivery; Multifunctional protein; Nanoparticle; Self-assembling