Tat peptide-mediated intracellular delivery of pharmaceutical nanocarriers.

Cell-penetrating peptides (CPPs) including TAT peptide (TATp) have been successfully used for intracellular delivery of a broad variety of cargoes including various nanoparticulate pharmaceutical carriers (liposomes, micelles, nanoparticles). Here, we will consider the main results in this area, with a special emphasis on TATp-mediated delivery of liposomes and DNA. We will also address the development of "smart" stimuli-sensitive nanocarriers, where cell-penetrating function can be activated by the decreased pH only inside the biological target minimizing thus the interaction of drug-loaded nanocarriers with non-target cells.

[1]  H. Maeda,et al.  Tumor vascular permeability and the EPR effect in macromolecular therapeutics: a review. , 2000, Journal of controlled release : official journal of the Controlled Release Society.

[2]  Allan Balmain,et al.  Cancer genetics: from Boveri and Mendel to microarrays , 2001, Nature Reviews Cancer.

[3]  W. Seeger,et al.  Nano-carriers for DNA delivery to the lung based upon a TAT-derived peptide covalently coupled to PEG-PEI. , 2005, Journal of controlled release : official journal of the Controlled Release Society.

[4]  R. G. Anderson The caveolae membrane system. , 1998, Annual review of biochemistry.

[5]  J. Rothbard,et al.  Role of membrane potential and hydrogen bonding in the mechanism of translocation of guanidinium-rich peptides into cells. , 2004, Journal of the American Chemical Society.

[6]  O. Haller,et al.  Antiviral state against influenza virus neutralized by microinjection of antibodies to interferon‐induced Mx proteins. , 1988, The EMBO journal.

[7]  S. Cryan,et al.  Increased intracellular targeting to airway cells using octaarginine-coated liposomes: in vitro assessment of their suitability for inhalation. , 2006, Molecular pharmaceutics.

[8]  R. Egleton,et al.  Bioavailability and Transport of Peptides and Peptide Drugs into the Brain , 1997, Peptides.

[9]  J. Gibbs Mechanism-based target identification and drug discovery in cancer research. , 2000, Science.

[10]  M. Woodle,et al.  Pharmacokinetics and anti‐tumor activity of vincristine encapsulated in sterically stabilized liposomes , 1995, International journal of cancer.

[11]  M. Johansson,et al.  Cell surface adherence and endocytosis of protein transduction domains. , 2003, Molecular therapy : the journal of the American Society of Gene Therapy.

[12]  Simon C Watkins,et al.  Efficiency of Protein Transduction Is Cell Type-dependent and Is Enhanced by Dextran Sulfate* , 2002, The Journal of Biological Chemistry.

[13]  M. Pooga,et al.  Cell penetration by transportan. , 1998, FASEB journal : official publication of the Federation of American Societies for Experimental Biology.

[14]  W. Shen,et al.  Mechanisms of TfR-mediated transcytosis and sorting in epithelial cells and applications toward drug delivery. , 2003, Advanced drug delivery reviews.

[15]  K. Wooley,et al.  Nanostructured materials designed for cell binding and transduction. , 2001, Biomacromolecules.

[16]  J. Whitton,et al.  Full-length proteins attached to the HIV tat protein transduction domain are neither transduced between cells, nor exhibit enhanced immunogenicity , 2002, Gene Therapy.

[17]  S. Gellman,et al.  Cytoplasmic and Nuclear Delivery of a TAT-derived Peptide and a β-Peptide after Endocytic Uptake into HeLa Cells* , 2003, Journal of Biological Chemistry.

[18]  Samuel Zalipsky,et al.  Tumor cell targeting of liposome-entrapped drugs with phospholipid-anchored folic acid-PEG conjugates. , 2004, Advanced drug delivery reviews.

[19]  E. Giralt,et al.  Mechanistic aspects of CPP-mediated intracellular drug delivery: relevance of CPP self-assembly. , 2006, Biochimica et biophysica acta.

[20]  Vladimir P Torchilin,et al.  Quantum dots spectrally distinguish multiple species within the tumor milieu in vivo , 2005, Nature Medicine.

[21]  R. Scheule,et al.  Basis of pulmonary toxicity associated with cationic lipid-mediated gene transfer to the mammalian lung. , 1997, Human gene therapy.

[22]  LeeAnn O. Bailey,et al.  Peptide-derivatized shell-cross-linked nanoparticles. 2. Biocompatibility evaluation. , 2004, Bioconjugate chemistry.

[23]  T. Bjørnholm,et al.  Functionalization and cellular uptake of boron carbide nanoparticles. The first step toward T cell-guided boron neutron capture therapy. , 2006, Bioconjugate chemistry.

[24]  Kinam Park,et al.  Controlled drug delivery : designing technologies for the future , 2000 .

[25]  V. Torchilin,et al.  Poly(ethylene glycol)-coated anti-cardiac myosin immunoliposomes: factors influencing targeted accumulation in the infarcted myocardium. , 1996, Biochimica et biophysica acta.

[26]  Ralph Weissleder,et al.  Transport Of Surface‐Modified Nanoparticles Through Cell Monolayers , 2005, Chembiochem : a European journal of chemical biology.

[27]  B. Katz Structural and mechanistic determinants of affinity and specificity of ligands discovered or engineered by phage display. , 1997, Annual review of biophysics and biomolecular structure.

[28]  M. Becker,et al.  Peptide-derivatized shell-cross-linked nanoparticles. 1. Synthesis and characterization. , 2004, Bioconjugate chemistry.

[29]  R Weissleder,et al.  Normal T-cell response and in vivo magnetic resonance imaging of T cells loaded with HIV transactivator-peptide-derived superparamagnetic nanoparticles. , 2001, Journal of immunological methods.

[30]  M. Monsigny,et al.  Membrane permeabilization and efficient gene transfer by a peptide containing several histidines. , 1998, Bioconjugate chemistry.

[31]  M. Giacca,et al.  Caveolae-mediated internalization of extracellular HIV-1 tat fusion proteins visualized in real time. , 2003, Molecular therapy : the journal of the American Society of Gene Therapy.

[32]  K. Jeang,et al.  Multifaceted Activities of the HIV-1 Transactivator of Transcription, Tat* , 1999, The Journal of Biological Chemistry.

[33]  J. V. Moran,et al.  Initial sequencing and analysis of the human genome. , 2001, Nature.

[34]  V. Torchilin,et al.  Targeted polymeric micelles for delivery of poorly soluble drugs , 2004, Cellular and Molecular Life Sciences CMLS.

[35]  R. Juliano,et al.  Intracellular Delivery of Oligonucleotide Conjugates and Dendrimer Complexes , 2006, Annals of the New York Academy of Sciences.

[36]  Glenn Walter,et al.  Rapid and effective labeling of brain tissue using TAT-conjugated CdS:Mn/ZnS quantum dots. , 2005, Chemical communications.

[37]  Steven F Dowdy,et al.  Transducible TAT-HA fusogenic peptide enhances escape of TAT-fusion proteins after lipid raft macropinocytosis , 2004, Nature Medicine.

[38]  T. Bártfai,et al.  VE-cadherin-derived cell-penetrating peptide, pVEC, with carrier functions. , 2001, Experimental cell research.

[39]  Mangay Williams,et al.  Superparamagnetic iron oxide particles transactivator protein-fluorescein isothiocyanate particle labeling for in vivo magnetic resonance imaging detection of cell migration: uptake and durability , 2003, Transplantation.

[40]  A. Prochiantz,et al.  Antennapedia homeobox peptide regulates neural morphogenesis. , 1991, Proceedings of the National Academy of Sciences of the United States of America.

[41]  A. Prochiantz,et al.  The third helix of the Antennapedia homeodomain translocates through biological membranes. , 1994, The Journal of biological chemistry.

[42]  Ulo Langel,et al.  Cell-penetrating peptides: mechanism and kinetics of cargo delivery. , 2005, Advanced drug delivery reviews.

[43]  V. Torchilin,et al.  TAT peptide on the surface of liposomes affords their efficient intracellular delivery even at low temperature and in the presence of metabolic inhibitors , 2001, Proceedings of the National Academy of Sciences of the United States of America.

[44]  B. Wiesner,et al.  Cellular uptake of an alpha-helical amphipathic model peptide with the potential to deliver polar compounds into the cell interior non-endocytically. , 1998, Biochimica et biophysica acta.

[45]  Joseph Rosenecker,et al.  Application of Novel Solid Lipid Nanoparticle (SLN)-Gene Vector Formulations Based on a Dimeric HIV-1 TAT-Peptide in Vitro and in Vivo , 2004, Pharmaceutical Research.

[46]  Jesus M de la Fuente,et al.  Tat peptide as an efficient molecule to translocate gold nanoparticles into the cell nucleus. , 2005, Bioconjugate chemistry.

[47]  F. Szoka,et al.  Thiocholesterol-based lipids for ordered assembly of bioresponsive gene carriers. , 2005, Molecular therapy : the journal of the American Society of Gene Therapy.

[48]  You Han Bae,et al.  TAT peptide-based micelle system for potential active targeting of anti-cancer agents to acidic solid tumors. , 2007, Journal of controlled release : official journal of the Controlled Release Society.

[49]  K. Hatanaka,et al.  Synthesis and evaluation of a novel lipid-peptide conjugate for functionalized liposome. , 2007, Bioorganic & medicinal chemistry letters.

[50]  V. Torchilin,et al.  "SMART" drug delivery systems: double-targeted pH-responsive pharmaceutical nanocarriers. , 2006, Bioconjugate chemistry.

[51]  E. Vivés,et al.  TAT peptide internalization: seeking the mechanism of entry. , 2003, Current protein & peptide science.

[52]  R Weissleder,et al.  High-efficiency intracellular magnetic labeling with novel superparamagnetic-Tat peptide conjugates. , 1999, Bioconjugate chemistry.

[53]  D. Piwnica-Worms,et al.  Evidence for a plasma membrane-mediated permeability barrier to Tat basic domain in well-differentiated epithelial cells: lack of correlation with heparan sulfate. , 2002, Biochemistry.

[54]  W. Jiskoot,et al.  Functional Characterization of an Endosome-disruptive Peptide and Its Application in Cytosolic Delivery of Immunoliposome-entrapped Proteins* , 2002, The Journal of Biological Chemistry.

[55]  Timothy B. Stockwell,et al.  The Sequence of the Human Genome , 2001, Science.

[56]  Maurice Green,et al.  Autonomous functional domains of chemically synthesized human immunodeficiency virus tat trans-activator protein , 1988, Cell.

[57]  K. Hruska,et al.  Protein transduction: unrestricted delivery into all cells? , 2000, Trends in cell biology.

[58]  V. Torchilin Recent advances with liposomes as pharmaceutical carriers , 2005, Nature Reviews Drug Discovery.

[59]  L. Chaloin,et al.  A new peptide vector for efficient delivery of oligonucleotides into mammalian cells. , 1997, Nucleic acids research.

[60]  Vladimir P Torchilin,et al.  Intracellular delivery of large molecules and small particles by cell-penetrating proteins and peptides. , 2005, Advanced drug delivery reviews.

[61]  R. Cortese Combinatorial libraries : synthesis, screening and application potential , 1996 .

[62]  S. Schwarze,et al.  In vivo protein transduction: intracellular delivery of biologically active proteins, compounds and DNA. , 2000, Trends in pharmacological sciences.

[63]  D. Porteous,et al.  HIV-1 Tat protein transduction domain peptide facilitates gene transfer in combination with cationic liposomes. , 2004, Journal of controlled release : official journal of the Controlled Release Society.

[64]  Kurt Ballmer-Hofer,et al.  Antennapedia and HIV Transactivator of Transcription (TAT) “Protein Transduction Domains” Promote Endocytosis of High Molecular Weight Cargo upon Binding to Cell Surface Glycosaminoglycans* , 2003, Journal of Biological Chemistry.

[65]  U. Nielsen,et al.  Tumor targeting using anti-her2 immunoliposomes. , 2001, Journal of controlled release : official journal of the Controlled Release Society.

[66]  W. Hong,et al.  Gene therapy for non-small cell lung cancer: a preliminary report of a phase I trial of adenoviral p53 gene replacement. , 1998, Seminars in oncology.

[67]  R. Schwendener,et al.  Enhanced heparan sulfate proteoglycan-mediated uptake of cell-penetrating peptide-modified liposomes , 2004, Cellular and Molecular Life Sciences CMLS.

[68]  R. Vandenbroucke,et al.  Cellular entry pathway and gene transfer capacity of TAT-modified lipoplexes. , 2007, Biochimica et biophysica acta.

[69]  D. Lasič,et al.  Liposomes: From Physics to Applications , 1993 .

[70]  T. N. Palmer,et al.  The mechanism of liposome accumulation in infarction. , 1984, Biochimica et biophysica acta.

[71]  M. Belting,et al.  Nuclear Targeting of Macromolecular Polyanions by an HIV-Tat Derived Peptide , 2002, The Journal of Biological Chemistry.

[72]  Carl O. Pabo,et al.  Cellular uptake of the tat protein from human immunodeficiency virus , 1988, Cell.

[73]  J. Lisziewicz,et al.  Antitat gene therapy: a candidate for late-stage AIDS patients. , 1995, Gene therapy.

[74]  G. Elliott,et al.  Intercellular Trafficking and Protein Delivery by a Herpesvirus Structural Protein , 1997, Cell.

[75]  I. Ojima,et al.  Recent advances in tumor-targeting anticancer drug conjugates. , 2005, Bioorganic & medicinal chemistry.

[76]  Y. Tseng,et al.  Translocation of liposomes into cancer cells by cell-penetrating peptides penetratin and tat: a kinetic and efficacy study. , 2002, Molecular pharmacology.

[77]  Ralph Weissleder,et al.  Differential conjugation of tat peptide to superparamagnetic nanoparticles and its effect on cellular uptake. , 2002, Bioconjugate chemistry.

[78]  J. Gibbs,et al.  Pharmaceutical research in molecular oncology , 1994, Cell.

[79]  V. Torchilin,et al.  p-Nitrophenylcarbonyl-PEG-PE-liposomes: fast and simple attachment of specific ligands, including monoclonal antibodies, to distal ends of PEG chains via p-nitrophenylcarbonyl groups. , 2001, Biochimica et biophysica acta.

[80]  V. Torchilin,et al.  Design, synthesis, and characterization of pH-sensitive PEG-PE conjugates for stimuli-sensitive pharmaceutical nanocarriers: the effect of substitutes at the hydrazone linkage on the ph stability of PEG-PE conjugates. , 2007, Bioconjugate chemistry.

[81]  H. Kamata,et al.  Amphiphilic peptides enhance the efficiency of liposome-mediated DNA transfection. , 1994, Nucleic acids research.

[82]  T K Sawyer,et al.  Src homology‐2 domains: Structure, mechanisms, and drug discovery , 1998, Biopolymers.

[83]  J. Rothbard,et al.  Adaptive translocation: the role of hydrogen bonding and membrane potential in the uptake of guanidinium-rich transporters into cells. , 2005, Advanced drug delivery reviews.

[84]  Vladimir P Torchilin,et al.  Cell transfection in vitro and in vivo with nontoxic TAT peptide-liposome–DNA complexes , 2003, Proceedings of the National Academy of Sciences of the United States of America.

[85]  Yanli Liu,et al.  Cellular trajectories of peptide-modified gold particle complexes: comparison of nuclear localization signals and peptide transduction domains. , 2004, Bioconjugate chemistry.

[86]  Ralph Weissleder,et al.  Tat peptide directs enhanced clearance and hepatic permeability of magnetic nanoparticles. , 2002, Bioconjugate chemistry.

[87]  Eric Vives,et al.  Cell-penetrating Peptides , 2003, The Journal of Biological Chemistry.

[88]  Vladimir P Torchilin,et al.  Enhanced transfection of tumor cells in vivo using “Smart” pH-sensitive TAT-modified pegylated liposomes , 2007, Journal of drug targeting.

[89]  Vladimir P Torchilin,et al.  TAT peptide-modified liposomes provide enhanced gene delivery to intracranial human brain tumor xenografts in nude mice. , 2006, Oncology research.

[90]  S. Hussain,et al.  Tumor suppressor genes: at the crossroads of molecular carcinogenesis, molecular epidemiology and human risk assessment. , 2001, Lung cancer.

[91]  A. Hoffman,et al.  A biomimetic pH-responsive polymer directs endosomal release and intracellular delivery of an endocytosed antibody complex. , 2002, Bioconjugate chemistry.

[92]  Steven F Dowdy,et al.  Cationic TAT peptide transduction domain enters cells by macropinocytosis. , 2005, Journal of controlled release : official journal of the Controlled Release Society.

[93]  M. Giacca,et al.  Internalization of HIV-1 Tat Requires Cell Surface Heparan Sulfate Proteoglycans* , 2001, The Journal of Biological Chemistry.

[94]  P. Workman New drug targets for genomic cancer therapy: successes, limitations, opportunities and future challenges. , 2001, Current cancer drug targets.

[95]  Ralph Weissleder,et al.  Tat peptide-derivatized magnetic nanoparticles allow in vivo tracking and recovery of progenitor cells , 2000, Nature Biotechnology.

[96]  Yao-Zhong Lin,et al.  Genetic engineering of proteins with cell membrane permeability , 1998, Nature Biotechnology.

[97]  M. Giacca,et al.  Cell Membrane Lipid Rafts Mediate Caveolar Endocytosis of HIV-1 Tat Fusion Proteins* , 2003, Journal of Biological Chemistry.

[98]  W. Jiskoot,et al.  OVCAR-3 cells internalize TAT-peptide modified liposomes by endocytosis. , 2004, Biochimica et biophysica acta.

[99]  V. Torchilin,et al.  siRNA-containing liposomes modified with polyarginine effectively silence the targeted gene , 2006, Journal of Controlled Release.

[100]  J. Suh,et al.  Gene delivery to differentiated neurotypic cells with RGD and HIV Tat peptide functionalized polymeric nanoparticles. , 2006, Biomaterials.

[101]  S. Futaki,et al.  Arginine-rich Peptides , 2001, The Journal of Biological Chemistry.

[102]  H. Farhood,et al.  The role of dioleoyl phosphatidylethanolamine in cationic liposome mediated gene transfer. , 1995, Biochimica et biophysica acta.

[103]  Priscille Brodin,et al.  A Truncated HIV-1 Tat Protein Basic Domain Rapidly Translocates through the Plasma Membrane and Accumulates in the Cell Nucleus* , 1997, The Journal of Biological Chemistry.

[104]  R. Weissleder,et al.  Labeling of immune cells for in vivo imaging using magnetofluorescent nanoparticles , 2006, Nature Protocols.

[105]  J. Hughes,et al.  Use of dithiodiglycolic acid as a tether for cationic lipids decreases the cytotoxicity and increases transgene expression of plasmid DNA in vitro. , 1999, Bioconjugate chemistry.

[106]  A. Zimmer,et al.  Drug delivery of oligonucleotides by peptides. , 2004, European journal of pharmaceutics and biopharmaceutics : official journal of Arbeitsgemeinschaft fur Pharmazeutische Verfahrenstechnik e.V.

[107]  S. Schuster,et al.  Transfer of monoclonal antibodies into mammalian cells by electroporation. , 1989, The Journal of biological chemistry.

[108]  N. Phillips,et al.  Toxicity and immunomodulatory activity of liposomal vectors formulated with cationic lipids toward immune effector cells. , 1997, Biochimica et biophysica acta.