Peptide-based carbon nanotubes for mitochondrial targeting.

In the present study, we report the design and synthesis of peptide-based-multi-walled carbon nanotubes (MWCNTs) to target mitochondria. Targeting these intracellular organelles might open the way to develop alternative systems to address diseases related to genetic mutations in mitochondrial (mt)-DNA, by delivering therapeutic oligonucleotides. The first step towards mitochondrial delivery of this type of nucleic acid was to target MWCNTs to mitochondria by covalent functionalization with a well-known endogenous mitochondrial targeting sequence (MTS). The subcellular localization of the conjugates, which were fluorescently labeled, in murine RAW 264.7 macrophages and human HeLa cells was then studied using different microscopy techniques, such as wide-field epifluorescence microscopy, confocal laser scanning microscopy (CLSM) and transmission electron microscopy (TEM). The localization of the MTS-MWCNT conjugates into mitochondria was further confirmed by analyzing the isolated organelles using TEM.

[1]  Maurizio Prato,et al.  Asbestos-like pathogenicity of long carbon nanotubes alleviated by chemical functionalization. , 2013, Angewandte Chemie.

[2]  Paul C. Wang,et al.  Single-walled carbon nanotubes alter cytochrome c electron transfer and modulate mitochondrial function. , 2012, ACS nano.

[3]  Feifan Zhou,et al.  Mitochondria-targeting photoacoustic therapy using single-walled carbon nanotubes. , 2012, Small.

[4]  M. Prato,et al.  Translocation mechanisms of chemically functionalised carbon nanotubes across plasma membranes. , 2012, Biomaterials.

[5]  Giuseppe Lamanna,et al.  Multifunctionalized carbon nanotubes as advanced multimodal nanomaterials for biomedical applications , 2011 .

[6]  Sandeep Kumar Vashist,et al.  Delivery of drugs and biomolecules using carbon nanotubes , 2011 .

[7]  Feifan Zhou,et al.  Mitochondria-targeting single-walled carbon nanotubes for cancer photothermal therapy. , 2011, Small.

[8]  M. Prato,et al.  Functional motor recovery from brain ischemic insult by carbon nanotube-mediated siRNA silencing , 2011, Proceedings of the National Academy of Sciences.

[9]  F. Toma,et al.  Potentiometric titration as a straightforward method to assess the number of functional groups on shortened carbon nanotubes , 2010 .

[10]  N. Bottini,et al.  Carbon nanotube-based nanocarriers: the importance of keeping it clean. , 2010, Journal of nanoscience and nanotechnology.

[11]  D. Tasis,et al.  Current progress on the chemical modification of carbon nanotubes. , 2010, Chemical reviews.

[12]  Feifan Zhou,et al.  New insights of transmembranal mechanism and subcellular localization of noncovalently modified single-walled carbon nanotubes. , 2010, Nano letters.

[13]  Huixin He,et al.  DNA and carbon nanotubes as medicine. , 2010, Advanced drug delivery reviews.

[14]  Giada Cellot,et al.  Carbon Nanotubes Carrying Cell‐Adhesion Peptides do not Interfere with Neuronal Functionality , 2009 .

[15]  M. Prato,et al.  Organic functionalisation and characterisation of single-walled carbon nanotubes. , 2009, Chemical Society reviews.

[16]  M. Prato,et al.  Cancer therapy: Small 10/2009 , 2009 .

[17]  M. Prato,et al.  Antitumor activity and prolonged survival by carbon-nanotube-mediated therapeutic siRNA silencing in a human lung xenograft model. , 2009, Small.

[18]  N. Bottini,et al.  Conjugation of antisense oligonucleotides to PEGylated carbon nanotubes enables efficient knockdown of PTPN22 in T lymphocytes. , 2009, Bioconjugate chemistry.

[19]  H. Harashima,et al.  Mitochondrial drug delivery systems for macromolecule and their therapeutic application to mitochondrial diseases. , 2008, Advanced drug delivery reviews.

[20]  S. Dimauro,et al.  Mitochondrial disorders in the nervous system. , 2008, Annual review of neuroscience.

[21]  H. Weiner,et al.  Delivery of drugs and macromolecules to mitochondria. , 2007, Advanced drug delivery reviews.

[22]  Walter Neupert,et al.  Why Do We Still Have a Maternally Inherited Mitochondrial DNA ? Insights from Evolutionary Medicine , 2007 .

[23]  T. Lithgow,et al.  Evolution of the Molecular Machines for Protein Import into Mitochondria , 2006, Science.

[24]  A. Khlobystov,et al.  Noncovalent interactions of molecules with single walled carbon nanotubes. , 2006, Chemical Society reviews.

[25]  Maurizio Prato,et al.  Double functionalization of carbon nanotubes for multimodal drug delivery. , 2006, Chemical communications.

[26]  V. Weissig,et al.  Mitochondrial leader sequence--plasmid DNA conjugates delivered into mammalian cells by DQAsomes co-localize with mitochondria. , 2005, Mitochondrion.

[27]  D. Wallace.  The mitochondrial genome in human adaptive radiation and disease: on the road to therapeutics and performance enhancement. , 2005, Gene.

[28]  Robert W. Taylor,et al.  Mitochondrial DNA mutations in human disease , 2005, Nature Reviews Genetics.

[29]  Vladimir P Torchilin,et al.  DQAsome-mediated delivery of plasmid DNA toward mitochondria in living cells. , 2003, Journal of controlled release : official journal of the Controlled Release Society.

[30]  M. Prato,et al.  Synthesis, structural characterization, and immunological properties of carbon nanotubes functionalized with peptides. , 2003, Journal of the American Chemical Society.

[31]  M. Prato,et al.  Amino acid functionalisation of water soluble carbon nanotubes. , 2002, Chemical communications.

[32]  E. Schon,et al.  Rescue of a deficiency in ATP synthesis by transfer of MTATP6, a mitochondrial DNA-encoded gene, to the nucleus , 2002, Nature Genetics.

[33]  V. Torchilin,et al.  DQAsome/DNA complexes release DNA upon contact with isolated mouse liver mitochondria. , 2001, Journal of controlled release : official journal of the Controlled Release Society.

[34]  Y. Kagawa,et al.  Gene therapy by mitochondrial transfer. , 2001, Advanced drug delivery reviews.

[35]  M. Prato,et al.  Novel versatile fullerene synthons. , 2001, The Journal of organic chemistry.

[36]  Robin A. J. Smith,et al.  Selective targeting of an antioxidant to mitochondria. , 1999, European journal of biochemistry.

[37]  D. Wallace.  Mitochondrial diseases in man and mouse. , 1999, Science.

[38]  D. Turnbull,et al.  Mammalian mitochondrial genetics: heredity, heteroplasmy and disease. , 1997, Trends in genetics : TIG.

[39]  G. Schatz.  The Protein Import System of Mitochondria* , 1996, The Journal of Biological Chemistry.

[40]  C Haanen,et al.  A novel assay for apoptosis. Flow cytometric detection of phosphatidylserine expression on early apoptotic cells using fluorescein labelled Annexin V. , 1995, Journal of immunological methods.

[41]  Gaetano Villani,et al.  Transfection of mitochondria: strategy towards a gene therapy of mitochondrial DNA diseases , 1995, Nucleic Acids Res..

[42]  S. Dimauro,et al.  A gene specifying subunit VIII of human cytochrome c oxidase is localized to chromosome 11 and is expressed in both muscle and non-muscle tissues. , 1989, The Journal of biological chemistry.

[43]  D. Vestweber,et al.  DNA-protein conjugates can enter mitochondria via the protein import pathway , 1989, Nature.

[44]  D. Wallace,et al.  Mitochondrial DNA mutation associated with Leber's hereditary optic neuropathy. , 1988, Science.

[45]  A. Harding,et al.  Deletions of muscle mitochondrial DNA in patients with mitochondrial myopathies , 1988, Nature.