title: Intracellular CXCR4⁺ cell targeting with T22-empowered protein-only nanoparticles.
abstract: BACKGROUND
  Cell-targeting peptides or proteins are appealing tools in nanomedicine and innovative medicines because they increase the local drug concentration and reduce potential side effects. CXC chemokine receptor 4 (CXCR4) is a cell surface marker associated with several severe human pathologies, including colorectal cancer, for which intracellular targeting agents are currently missing.
  
  
  RESULTS
  Four different peptides that bind CXCR4 were tested for their ability to internalize a green fluorescent protein-based reporter nanoparticle into CXCR4⁺ cells. Among them, only the 18 mer peptide T22, an engineered segment derivative of polyphemusin II from the horseshoe crab, efficiently penetrated target cells via a rapid, receptor-specific endosomal route. This resulted in accumulation of the reporter nanoparticle in a fully fluorescent and stable form in the perinuclear region of the target cells, without toxicity either in cell culture or in an in vivo model of metastatic colorectal cancer.
  
  
  CONCLUSIONS
  Given the urgent demand for targeting agents in the research, diagnosis, and treatment of CXCR4-linked diseases, including colorectal cancer and human immunodeficiency virus infection, T22 appears to be a promising tag for the intracellular delivery of protein drugs, nanoparticles, and imaging agents.
authors.affiliation: Institut de Biotecnologia i de Biomedicina, Universitat Autònoma de Barcelona, Bellaterra, Barcelona, Spain.
authors.forename: Ugutz
authors.initials: U
authors.lastname: Unzueta
authors.forename: María Virtudes
authors.initials: MV
authors.lastname: Céspedes
authors.forename: Neus
authors.initials: N
authors.lastname: Ferrer-Miralles
authors.forename: Isolda
authors.initials: I
authors.lastname: Casanova
authors.forename: Juan
authors.initials: J
authors.lastname: Cedano
authors.forename: José Luis
authors.initials: JL
authors.lastname: Corchero
authors.forename: Joan
authors.initials: J
authors.lastname: Domingo-Espín
authors.forename: Antonio
authors.initials: A
authors.lastname: Villaverde
authors.forename: Ramón
authors.initials: R
authors.lastname: Mangues
authors.forename: Esther
authors.initials: E
authors.lastname: Vázquez
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D045744:Cell Line, Tumor; D016503:Drug Delivery Systems / Q000379:methods*; D004705:Endocytosis / Q000502:physiology; D005260:Female; D049452:Green Fluorescent Proteins / Q000737:chemistry / Q000493:pharmacokinetics; D006801:Humans; D042541:Intracellular Space / Q000378:metabolism*; D051379:Mice; D008856:Microscopy, Fluorescence; D008958:Models, Molecular; D008969:Molecular Sequence Data; D053758:Nanoparticles / Q000737:chemistry*; D010455:Peptides / Q000737:chemistry / Q000493:pharmacokinetics*; D019718:Receptors, CXCR4 / Q000378:metabolism*; D011993:Recombinant Fusion Proteins / Q000737:chemistry / Q000493:pharmacokinetics
chemical_list: C527276:CXCR4 protein, human; D010455:Peptides; D019718:Receptors, CXCR4; D011993:Recombinant Fusion Proteins; C516580:T22 peptide; D049452:Green Fluorescent Proteins