Mitochondrial Nanotechnology for Cancer Therapy

  • Volkmar Weissig
  • Gerard G. M. D’Souza
  • Shing-Ming Cheng
  • Sarathi Boddapati


The tight association of mitochondrial dysfunction with the pathogenesis of cancer has been the subject of preceding chapters in this book. It has been made evident that a rapidly growing insight into the link between cancer and mitochondrial functions is the basis for identifying new molecular sites at or inside mitochondria that potentially present novel drug targets for pharmacological intervention. Subsequently, the mitochondrial network as an emerging target of anticancer therapy has been the subject of another chapter in this book. The development of pharmacological agents specifically aimed at compromising the structural and functional integrity of mitochondria materializes as a new approach to combat cancer cell proliferation. Already, a large variety of chemically diverse small molecules have been demonstrated to have direct effects on mitochondrial morphology and functions, either at the DNA level or upon targeting proteins located in the inner or outer...


Betulinic Acid Mitochondrial Target Phospholipid Vesicle Free Paclitaxel Archaeal Lipid 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.


  1. Andre N, Braguer D, Brasseur G, Goncalves A, Lemesle-Meunier D, et al. 2000. Paclitaxel induces release of cytochrome c from mitochondria isolated from human neuroblastoma cells. Cancer Res 60: 5349–53PubMedGoogle Scholar
  2. Andre N, Carre M, Brasseur G, Pourroy B, Kovacic H, et al. 2002. Paclitaxel targets mitochondria upstream of caspase activation in intact human neuroblastoma cells. FEBS Lett 532: 256–60CrossRefPubMedGoogle Scholar
  3. Azzazy HM, Mansour MM, Kazmierczak SC. 2006. Nanodiagnostics: a new frontier for clinical laboratory medicine. Clin Chem 52: 1238–46CrossRefPubMedGoogle Scholar
  4. Bangham AD, Standish MM, Watkins JC. 1965a. Diffusion of univalent ions across the lamellae of swollen phospholipids. J Mol Biol 13: 238–52CrossRefGoogle Scholar
  5. Bangham AD, Standish MM, Weissmann G. 1965b. The action of steroids and streptolysin S on the permeability of phospholipid structures to cations. J Mol Biol 13: 253–9CrossRefGoogle Scholar
  6. Boddapati SV, Tongcharoensirikul P, Hanson RN, D'Souza GG, Torchilin VP, Weissig V. 2005. Mitochondriotropic liposomes. J Liposome Res 15: 49–58PubMedGoogle Scholar
  7. Carre M, Carles G, Andre N, Douillard S, Ciccolini J, et al. 2002. Involvement of microtubules and mitochondria in the antagonism of arsenic trioxide on paclitaxel-induced apoptosis. Biochem Pharmacol 63: 1831–42CrossRefPubMedGoogle Scholar
  8. Cheng SM, Pabba S, Torchilin VP, Fowle W, Kimpfler A, Schubert R, Weissig V. 2005. Towards mitochondria-specific delivery of apoptosis-inducing agents: DQAsomal incorporated paclitaxel. J Drug Deliv Sci Technol 15: 81–6Google Scholar
  9. Cheng SM, Boddapati SV, D'Souza GM, Weissig V. 2007. DQAsomes as Mitochondria-Targeted Nano-Carriers for Anticancer Drugs. In Amiji, pp. M Nanotechnology for Cancer Therapeutics, ed. CRC/Taylor & Francis Group LLCFL, USA/PA, USA: 787–802.Google Scholar
  10. Costantini P, Jacotot E, Decaudin D, Kroemer G. 2000a. Mitochondrion as a novel target of anticancer chemotherapy. J Natl Cancer Inst 92: 1042–53CrossRefGoogle Scholar
  11. Costantini P, Jacotot E, Decaudin D, Kroemer G. 2000b. Mitochondrion as a novel target of anticancer chemotherapy. J Natl Cancer Inst 92: 1042–53CrossRefGoogle Scholar
  12. Dauty E, Verkman AS. 2005. Actin cytoskeleton as the principal determinant of size-dependent DNA mobility in cytoplasm: a new barrier for non-viral gene delivery. J Biol Chem 280: 7823–8CrossRefPubMedGoogle Scholar
  13. Dias N, Bailly C. 2005. Drugs targeting mitochondrial functions to control tumor cell growth. Biochem Pharmacol 70: 1–12CrossRefPubMedGoogle Scholar
  14. D'Souza GG, Rammohan R, Cheng SM, Torchilin VP, Weissig V. 2003. DQAsome-mediated delivery of plasmid DNA toward mitochondria in living cells. J Control Release 92: 189–97CrossRefPubMedGoogle Scholar
  15. D'Souza GG, Boddapati SV, Weissig V. 2005. Mitochondrial leader sequence-plasmid DNA conjugates delivered into mammalian cells by DQAsomes co-localize with mitochondria. Mitochondrion 5: 352–8CrossRefPubMedGoogle Scholar
  16. D'Souza GG, Boddapati SV, Weissig V. 2007. Gene therapy of the other genome: the challenges of treating mitochondrial DNA defects. Pharm Res 24: 228–38CrossRefPubMedGoogle Scholar
  17. Everts M. 2007. Thermal scalpel to target cancer. Expert Rev Med Devices 4: 131–6CrossRefPubMedGoogle Scholar
  18. Fantin VR, Berardi MJ, Scorrano L, Korsmeyer SJ, Leder P. 2002. A novel mitochondriotoxic small molecule that selectively inhibits tumor cell growth. Cancer Cell 2: 29–42CrossRefPubMedGoogle Scholar
  19. Ferlini C, Raspaglio G, Mozzetti S, Distefano M, Filippetti F, et al. 2003. Bcl-2 Down-Regulation Is a Novel Mechanism of Paclitaxel Resistance. Mol Pharmacol 64: 51–8CrossRefPubMedGoogle Scholar
  20. Fujino M, Li XK, Kitazawa Y, Guo L, Kawasaki M, et al. 2002. Distinct pathways of apoptosis triggered by FTY720, etoposide, and anti-Fas antibody in human T-lymphoma cell line (Jurkat cells). J Pharmacol Exp Ther 300: 939–45CrossRefPubMedGoogle Scholar
  21. Fulda S, Susin SA, Kroemer G, Debatin KM. 1998. Molecular ordering of apoptosis induced by anticancer drugs in neuroblastoma cells. Cancer Res 58: 4453–60PubMedGoogle Scholar
  22. Gambacorta A, Gliozi A, Rosa M. De1995. Archaeal lipids and their biotechnological applications. World J Microbiol Biotechnol 11: 115–31CrossRefGoogle Scholar
  23. Hockenbery DM. 2002. A mitochondrial Achilles' heel in cancer? Cancer Cell 2: 1–2CrossRefPubMedGoogle Scholar
  24. Horobin RW. 2001. Uptake, distribution and accumulation of dyes and fluorescent probes within living cells: a structure-activity modelling approach. Adv Colour Sci Technol 4: 101–7Google Scholar
  25. Horobin RW, Trapp S, Weissig V. 2007. Mitochondriotropics: a review of their mode of action, and their application fro drug and DNA delivery to mammalian mitochondria. J Control Release 121125–136:CrossRefPubMedGoogle Scholar
  26. Itoh M, Noutomi T, Toyota H, Mizuguchi J. 2003. Etoposide-mediated sensitization of squamous cell carcinoma cells to tumor necrosis factor-related apoptosis-inducing ligand (TRAIL)-induced loss in mitochondrial membrane potential. Oral Oncol 39: 269–76CrossRefPubMedGoogle Scholar
  27. Ju-Nam Y, Bricklebank N, Allen DW, Gardiner PH, Light ME, Hursthouse MB. 2006. Phosphonioalkylthiosulfate zwitterions – new masked thiol ligands for the formation of cationic functionalised gold nanoparticles. Org Biomol Chem 4: 4345–51CrossRefPubMedGoogle Scholar
  28. Kidd JF, Pilkington MF, Schell MJ, Fogarty KE, Skepper JN, et al. 2002. Paclitaxel affects cytosolic calcium signals by opening the mitochondrial permeability transition pore. J Biol Chem 277: 6504–10CrossRefPubMedGoogle Scholar
  29. Lasch J, Meye A, Taubert H, Koelsch R, Mansa-ard J, Weissig V. 1999. Dequalinium vesicles form stable complexes with plasmid DNA which are protected from DNase attack. Biol Chem 380: 647–52CrossRefPubMedGoogle Scholar
  30. Lukacs GL, Haggie P, Seksek O, Lechardeur D, Freedman N, Verkman AS. 2000. Size-dependent DNA mobility in cytoplasm and nucleus. J Biol Chem 275: 1625–9CrossRefPubMedGoogle Scholar
  31. Maeda H, Wu J, Sawa T, Matsumura Y, Hori K. 2000. Tumor vascular permeability and the EPR effect in macromolecular therapeutics: a review. J Control Release 65: 271–84CrossRefPubMedGoogle Scholar
  32. Marchetti P, Zamzami N, Joseph B, Schraen-Maschke S, Mereau-Richard C, et al. 1999. The novel retinoid 6-[3-(1-adamantyl)-4-hydroxyphenyl]-2-naphtalene carboxylic acid can trigger apoptosis through a mitochondrial pathway independent of the nucleus. Cancer Res 59: 6257–66PubMedGoogle Scholar
  33. Matsumura Y. 2007. Preclinical and clinical studies of anticancer drug-incorporated polymeric micelles. J Drug Target 15: 507–17CrossRefPubMedGoogle Scholar
  34. Matsumura Y, Oda T, Maeda H. 1987. [General mechanism of intratumor accumulation of macromolecules: advantage of macromolecular therapeutics]. Gan To Kagaku Ryoho 14: 821–9PubMedGoogle Scholar
  35. Medda R, Jakobs S, Hell SW, Bewersdorf J. 2006. 4Pi microscopy of quantum dot-labeled cellular structures. J Struct Biol 156: 517–23CrossRefPubMedGoogle Scholar
  36. Niedermann G, Weissig V, Sternberg B, Lasch J. 1991. Carboxyacyl derivatives of cardiolipin as four-tailed hydrophobic anchors for the covalent coupling of hydrophilic proteins to liposomes. Biochim Biophys Acta 1070: 401–8CrossRefPubMedGoogle Scholar
  37. Rowe TC, Weissig V, Lawrence JW. 2001. Mitochondrial DNA metabolism targeting drugs. Adv Drug Deliv Rev 49: 175–87CrossRefPubMedGoogle Scholar
  38. Seksek O, Biwersi J, Verkman AS. 1997. Translational diffusion of macromolecule-sized solutes in cytoplasm and nucleus. J Cell Biol 138: 131–42CrossRefPubMedGoogle Scholar
  39. Torchilin VP, Weissig V, Martin FJ, Heath TD, New RRC. 2003. Surface Modification of Liposomes. In Torchilin, VP Weissig, V, Liposomes – A Practical Approach, ed. Oxford University pressOxford: pp. 193–230.Google Scholar
  40. Trapp S, Horobin RW. 2005. A predictive model for the selective accumulation of chemicals in tumor cells. Eur Biophys J 34: 959–66CrossRefPubMedGoogle Scholar
  41. Vaughan EE, Dean DA. 2006. Intracellular trafficking of plasmids during transfection is mediated by microtubules. Mol Ther 13: 422–8CrossRefPubMedGoogle Scholar
  42. Weissig V, Gregoriadis G. 1993. Coupling of Aminogroup-Bearing Ligands to Liposomes. In Gregoriadis, pp. G Liposome Technology, ed. CRCBoca Raton, Ann Arbor, London, Tokyo: 231–48.Google Scholar
  43. Weissig V, Lasch J, Klibanov AL, Torchilin VP. 1986. A new hydrophobic anchor for the attachment of proteins to liposomal membranes. FEBS Lett 202: 86–90CrossRefPubMedGoogle Scholar
  44. Weissig V, Lasch J, Gregoriadis G. 1989. Covalent coupling of sugars to liposomes. Biochim Biophys Acta 1003: 54–7PubMedGoogle Scholar
  45. Weissig V, Lasch J, Erdos G, Meyer HW, Rowe TC, Hughes J. 1998. DQAsomes: a novel potential drug and gene delivery system made from Dequalinium. Pharm Res 15: 334–7CrossRefPubMedGoogle Scholar
  46. Weissig V, Lizano C, Torchilin VP. 2000. Selective DNA release from DQAsome/DNA complexes at mitochondria-like membranes. Drug Deliv 7: 1–5CrossRefPubMedGoogle Scholar
  47. Weissig V, D'Souza GG, Torchilin VP. 2001. DQAsome/DNA complexes release DNA upon contact with isolated mouse liver mitochondria. J Control Release 75: 401–8CrossRefPubMedGoogle Scholar
  48. Weissig V, Cheng S-M, D'Souza G. 2004. Mitochondrial Pharmaceutics. Mitochondrion 3: 229–44CrossRefPubMedGoogle Scholar
  49. Weissig V, Boddapati SV, D'Souza GGM, Horobin RH. 2007a. Functionalization of Pharmaceutical Nanocarriers for Mitochondria-targeted Drug and DNA Delivery. InMultifunctional Pharmaceutical Nanocarriers, ed. VP Torchilin: Springer: BerlinGoogle Scholar
  50. Weissig V, Boddapati SV, Jabre L, D'Souza GGM. 2007b. Mitochondria-specific nanotechnology. Nanomedicine 2: 275–85CrossRefGoogle Scholar
  51. Zorov DB, Kobrinsky E, Juhaszova M, Sollott SJ. 2004. Examining intracellular organelle function using fluorescent probes: from animalcules to quantum dots. Circ Res 95: 239–52CrossRefPubMedGoogle Scholar

Copyright information

© Springer Science + Business Media, LLC 2009

Authors and Affiliations

  • Volkmar Weissig
    • 1
  • Gerard G. M. D’Souza
  • Shing-Ming Cheng
  • Sarathi Boddapati
  1. 1.Department of Pharmaceutical SciencesMidwestern University College of Pharmacy GlendaleGlendaleUSA

Personalised recommendations