Skip to main content
SpringerLink
Log in

Accessing Mitochondrial Targets Using NanoCargos

  • Chapter
  • First Online:
Book cover Intracellular Delivery III

Part of the book series: Fundamental Biomedical Technologies ((FBMT))

Abstract

Mitochondria are membrane bound organelles that play essential roles for cell life, including energy production, apoptosis, redox balance, and regulation of calcium. Mitochondrial dysfunction is a hallmark for various diseases ranging from well-known diseases like cancer to rare genetic disorders like Barth’s syndrome. Accordingly, mitochondria have been identified as key targets for therapeutic intervention. Mitochondria targeting strategies using nanocargos are rapidly growing tools for delivery of therapeutic and/or diagnostic payloads to mitochondria. In this chapter, we will highlight specific mitochondrial targets for nanotechnology-based delivery vehicles, NanoCargos, and discuss intracellular uptake mechanisms for NanoCargos, as well as technological methods for investigating mechanism for NanoCargo internalization into mitochondria.

This is a preview of subscription content, log in via an institution to check access.

Access this chapter

Log in via an institution
Chapter
USD 29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 129.00
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 169.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info
Hardcover Book
USD 169.99
Price excludes VAT (USA)
  • Durable hardcover edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

Abbreviations

AFM:

Atomic force microscopy

ANT:

Adenosine nucleotide translocator

ATP:

Adenosine triphosphate

CPP:

Cell-penetrating peptide

CDs:

Carbon dots

CPZ:

Chlorpromazine

DOX:

Doxorubicin

FCCP:

Carbonylcyanide-p-(trifluoromethoxy)phenylhydrazone

FRET:

Förster Resonance Energy Transfer

GQDs:

Graphene quantum dots

HDL:

High density lipoprotein

HGC:

Hydrophobic modified glycol chitosan

HK:

Hexokinase

ICP-MS:

Inductively coupled plasma mass spectrometry

IMM:

Inner mitochondrial membrane

IMS:

Intermembrane space

IVIS:

In vivo image system

JC-1:

5,5’6,6’-tetrachloro-1,1’,3,3’-tetraethylbenzimidazolcarbocyanine iodide

LDH:

Layered double hydroxide

MM:

Mitochondrial matrix

mPTPC:

Mitochondrial permeability transition pore complex

mtDNA:

Mitochondrial DNA

MTS:

Mitochondria targeting sequence

nDNA:

Nuclear DNA

OMM:

Outer mitochondrial membrane

OXPHOS:

Oxidative phosphorylation

PEG:

Polyethyleneglycol

QDs:

Quantum dots

ROS:

Reactive oxygen species

SEM:

Scanning electron microscopy

SERS:

Surface-enhanced Raman scattering

TEM:

Transmission electron microscopy

TPP:

Triphenyphosphonium cation

TMRM:

Tetramethylrhodamine methyl ester

TMRE:

Tetramethylrhodamine ethyl ester

VDAC:

Voltage dependent anion channel

References

  • Agnello M, Morici G, Rinaldi AM (2008) A method for measuring mitochondrial mass and activity. Cytotechnology 56(3):145–149

    Article  PubMed  PubMed Central  Google Scholar 

  • Andersen H, Parhamifar L, Moghimi SM (2014) Uptake and intracellular trafficking of nanocarriers. In: Prokop A, Iwasaki Y, Harada A (eds) Intracellular delivery II: fundamentals and applications, 1st edn. Springer, Dordrecht, pp 117–138

    Google Scholar 

  • Armstrong JS (2006) Mitochondria: a target for cancer therapy. Br J Pharmacol 147(3):239–248

    Article  CAS  PubMed  Google Scholar 

  • Basarkar A, Singh J (2009) Poly (lactide-co-glycolide)-polymethacrylate nanoparticles for intramuscular delivery of plasmid encoding interleukin-10 to prevent autoimmune diabetes in mice. Pharm Res 26(1):72–81

    Article  CAS  PubMed  Google Scholar 

  • Bernas T, Robinson JP, Asem EK, Rajwa B (2005) Loss of image quality in photobleaching during microscopic imaging of fluorescent probes bound to chromatin. J Biomed Opt 10(6):064015-064015-9

    Google Scholar 

  • Boddapati SV, D’Souza GGM, Erdogan S, Torchilin VP, Weissig V (2008) Organelle-targeted nanocarriers: specific delivery of liposomal ceramide to mitochondria enhances its cytotoxicity in vitro and in vivo. Nano Lett 8(8):2559–2563

    Article  CAS  PubMed  Google Scholar 

  • Brandon M, Baldi P, Wallace DC (2006) Mitochondrial mutations in cancer. Oncogene 25(34):4647–4662

    Article  CAS  PubMed  Google Scholar 

  • Bressan E, Ferroni L, Gardin C, Rigo C, Stocchero M, Vindigni V, Cairns W, Zavan B (2013) Silver nanoparticles and mitochondrial interaction. Int Dent J 2013:312747

    Google Scholar 

  • Buckman JF, Hernández H, Kress GJ, Votyakova TV, Pal S, Reynolds IJ (2001) MitoTracker labeling in primary neuronal and astrocytic cultures: influence of mitochondrial membrane potential and oxidants. J Neurosci Methods 104(2):165–176

    Article  CAS  PubMed  Google Scholar 

  • Chakraborty A, Jana NR (2015) Design and synthesis of triphenylphosphonium functionalized nanoparticle probe for mitochondria targeting and imaging. J Phys Chem C 119(5):2888–2895

    CAS  Google Scholar 

  • Chatterjee A, Mambo E, Sidransky D (2006) Mitochondrial DNA mutations in human cancer. Oncogene 25(34):4663–4674

    Article  CAS  PubMed  Google Scholar 

  • Chazotte B (2009) Labeling mitochondria with fluorescent dyes for imaging. Dig Cold Spring Harb Protoc. doi:10.1101/pdb.prot4948.

    Google Scholar 

  • Chen Y, Dorn GW (2013) PINK1-phosphorylated mitofusin 2 is a Parkin receptor for culling damaged mitochondria. Science 340(6131):471–475

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Chen H-H, Chien C-C, Petibois C, Wang C-L, Chu YS, Lai S-F, Hua T-E, Chen Y-Y, Cai X, Kempson IM (2011) Quantitative analysis of nanoparticle internalization in mammalian cells by high resolution X-ray microscopy. J Nanobiotechnol 9(14). doi:10.1186/1477-3155-9-14

    Google Scholar 

  • Chong Y, Ma Y, Shen H, Tu X, Zhou X, Xu J, Dai J, Fan S, Zhang Z (2014) The in vitro and in vivo toxicity of graphene quantum dots. Biomaterials 35(19):5041–5048

    Article  CAS  PubMed  Google Scholar 

  • Clancy B, Cauller L (1998) Reduction of background autofluorescence in brain sections following immersion in sodium borohydride. J Neurosci Methods 83(2):97–102

    Article  CAS  PubMed  Google Scholar 

  • Cooper GM (2000) The cell – a molecular approach, 2nd edn. Sinauer Associates, Sunderland

    Google Scholar 

  • Cossarizza A, Baccaranicontri M, Kalashnikova G, Franceschi C (1993) A New method for the cytofluorometric analysis of mitochondrial membrane potential using the J-aggregate forming lipophilic cation 5,5′,6,6′-tetrachloro-1,1′,3,3′-tetraethylbenzimidazolcarbocyanine iodide (JC-1). Biochem Biophys Res Commun 197(1):40–45

    Article  CAS  PubMed  Google Scholar 

  • Damgé C, Socha M, Ubrich N, Maincent P (2010) Poly (ε‐caprolactone)/eudragit nanoparticles for oral delivery of aspart‐insulin in the treatment of diabetes. J Pharm Sci 99(2):879–889

    Article  PubMed  CAS  Google Scholar 

  • Dausend J, Musyanovych A, Dass M, Walther P, Schrezenmeier H, Landfester K, Mailänder V (2008) Uptake mechanism of oppositely charged fluorescent nanoparticles in HeLa cells. Macromol Biosci 8(12):1135–1143

    Article  CAS  PubMed  Google Scholar 

  • Deshayes S, Morris M, Divita G, Heitz F (2005) Cell-penetrating peptides: tools for intracellular delivery of therapeutics. Cell Mol Life Sci 62(16):1839–1849

    Article  CAS  PubMed  Google Scholar 

  • Dimauro S, Davidzon G (2005) Mitochondrial DNA and disease. Ann Med 37(3):222–232

    Article  CAS  PubMed  Google Scholar 

  • DiMauro S, Andreu AL, Musumeci O, Bonilla E (2001) Diseases of oxidative phosphorylation due to mtDNA mutations. Semin Neurol 21(3):251–260

    Article  CAS  PubMed  Google Scholar 

  • Doherty GJ, McMahon HT (2009) Mechanisms of endocytosis. Annu Rev Biochem 78:857–902

    Article  CAS  PubMed  Google Scholar 

  • Endo T, Yamano K (2009) Multiple pathways for mitochondrial protein traffic. Biol Chem 390(8):723–730

    Article  CAS  PubMed  Google Scholar 

  • Ernster L, Schatz G (1981) Mitochondria: a historical review. J Cell Biol 91(3):227–255

    Article  CAS  PubMed Central  Google Scholar 

  • Fadeel B, Ottosson A, Pervaiz S (2008) Big wheel keeps on turning: apoptosome regulation and its role in chemoresistance. Cell Death Differ 15(3):443–452

    Article  CAS  PubMed  Google Scholar 

  • Federico A, Cardaioli E, Da Pozzo P, Formichi P, Gallus GN, Radi E (2012) Mitochondria, oxidative stress and neurodegeneration. J Neurol Sci 322(1–2):254–262

    Article  CAS  PubMed  Google Scholar 

  • Feldhaeusser B, Platt SR, Marrache S, Kolishetti N, Pathak RK, Montgomery DJ, Reno LR, Howerth E, Dhar S (2015) Evaluation of nanoparticle delivered cisplatin in beagles. Nanoscale 7(33):13822–13830

    Article  CAS  PubMed  Google Scholar 

  • Fernando LP, Kandel PK, Yu J, McNeill J, Ackroyd PC, Christensen KA (2010) Mechanism of cellular uptake of highly fluorescent conjugated polymer nanoparticles. Biomacromolecules 11(10):2675–2682

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Flemming N, Gallo L, Forbes JM, Ward MS (2015) Tapping into mitochondria to find novel targets for diabetes complications. Curr Drug Targets 17(12):1341–1349

    Google Scholar 

  • Fontana G, Licciardi M, Mansueto S, Schillaci D, Giammona G (2001) Amoxicillin-loaded polyethylcyanoacrylate nanoparticles: Influence of PEG coating on the particle size, drug release rate and phagocytic uptake. Biomaterials 22(21):2857–2865

    Article  CAS  PubMed  Google Scholar 

  • Friedman JR, Nunnari J (2014) Mitochondrial form and function. Nature 505(7483):335–343

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Gilmore K, Wilson M (1999) The use of chloromethyl-X-rosamine (Mitotracker red) to measure loss of mitochondrial membrane potential in apoptotic cells is incompatible with cell fixation. Cytometry 36(4):355–358

    Article  CAS  PubMed  Google Scholar 

  • Greenamyre JT, Hastings TG (2004) Parkinson’s–divergent causes, convergent mechanisms. Science 304(5674):1120–1122

    Article  CAS  PubMed  Google Scholar 

  • Halperin F, Lopez X, Manning R, Kahn CR, Kulkarni RN, Goldfine AB (2012) Insulin augmentation of glucose-stimulated insulin secretion is impaired in insulin-resistant humans. Diabetes 61(2):301–309

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Han JY, Kang MJ, Kim KH, Han PL, Kim HS, Ha JY, Son JH (2015) Nitric oxide induction of Parkin translocation in PTEN-induced putative kinase 1 (PINK1) deficiency: functional role of neuronal nitric oxide synthase during mitophagy. J Biol Chem 290(16):10325–10335

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Hanahan D, Weinberg RA (2011) Hallmarks of cancer: the next generation. Cell 144(5):646–674

    Article  CAS  PubMed  Google Scholar 

  • Harush-Frenkel O, Debotton N, Benita S, Altschuler Y (2007) Targeting of nanoparticles to the clathrin-mediated endocytic pathway. Biochem Biophys Res Commun 353(1):26–32

    Article  CAS  PubMed  Google Scholar 

  • Herce H, Garcia A, Litt J, Kane R, Martin P, Enrique N, Rebolledo A, Milesi V (2009) Arginine-rich peptides destabilize the plasma membrane, consistent with a pore formation translocation mechanism of cell-penetrating peptides. Biophys J 97(7):1917–1925

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Hill JH, Chen Z, Xu H (2014) Selective propagation of functional mitochondrial DNA during oogenesis restricts the transmission of a deleterious mitochondrial variant. Nat Genet 46(4):389–392

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Houtkooper RH, Vaz FM (2008) Cardiolipin, the heart of mitochondrial metabolism. Cell Mol Life Sci 65(16):2493–2506

    Article  CAS  PubMed  Google Scholar 

  • Iversen TG, Frerker N, Sandvig K (2012) Uptake of ricinB-quantum dot nanoparticles by a macropinocytosis-like mechanism. J Nanobiotechnology 10(1): 33

    Google Scholar 

  • Kalathil AA, Kumar A, Banik B, Ruiter TA, Pathak RK, Dhar S (2016) New formulation of old aspirin for better delivery. Chem Commun 52(1):140–143

    Article  CAS  Google Scholar 

  • Karataş ÖF, Sezgin E, Aydın Ö, Çulha M (2009) Interaction of gold nanoparticles with mitochondria. Colloids Surf B 71(2):315–318

    Article  CAS  Google Scholar 

  • Kazlauskaite A, Muqit MM (2015) PINK1 and Parkin – mitochondrial interplay between phosphorylation and ubiquitylation in Parkinson's disease. FEBS J 282(2):215–223

    Article  CAS  PubMed  Google Scholar 

  • Keij JF, Bell‐Prince C, Steinkamp JA (2000) Staining of mitochondrial membranes with 10‐nonyl acridine orange MitoFluor Green, and MitoTracker Green is affected by mitochondrial membrane potential altering drugs. Cytometry 39(3):203–210

    Article  CAS  PubMed  Google Scholar 

  • Klein ND, Hurley KR, Feng ZV, Haynes CL (2015) Dark field transmission electron microscopy as a tool for identifying inorganic nanoparticles in biological matrices. Anal Chem 87(8):4356–4362

    Article  CAS  PubMed  Google Scholar 

  • Kroemer G (2006) Mitochondria in cancer. Oncogene 25(34):4630–4632

    Article  CAS  PubMed  Google Scholar 

  • Kwon HJ, Cha M-Y, Kim D, Kim DK, Soh M, Shin K, Hyeon T, Mook-Jung I (2016) Mitochondria-targeting ceria nanoparticles as antioxidants for Alzheimer’s disease. ACS Nano 10(2):2860–2870

    Article  CAS  PubMed  Google Scholar 

  • Li SP-Y, Lau CT-S, Louie M-W, Lam Y-W, Cheng SH, Lo KK-W (2013) Mitochondria-targeting cyclometalated iridium (III)–PEG complexes with tunable photodynamic activity. Biomaterials 34(30):7519–7532

    Article  CAS  PubMed  Google Scholar 

  • Lim JP, Gleeson PA (2011) Macropinocytosis: an endocytic pathway for internalising large gulps. Immunol Cell Biol 89(8):836–843

    Article  CAS  PubMed  Google Scholar 

  • Lim SY, Shen W, Gao Z (2015) Carbon quantum dots and their applications. Chem Soc Rev 44(1):362–381

    Article  CAS  PubMed  Google Scholar 

  • Lindgren M, Hällbrink M, Prochiantz A, Langel Ü (2000) Cell-penetrating peptides. Trends Pharmacol Sci 21(3):99–103

    Article  CAS  PubMed  Google Scholar 

  • Madani F, Lindberg S, Langel Ü, Futaki S, Gräslund A (2011) Mechanisms of cellular uptake of cell-penetrating peptides. Dig Biophys J. doi:10.1155/2011/414729

    Google Scholar 

  • Marrache S, Dhar S (2012) Engineering of blended nanoparticle platform for delivery of mitochondria-acting therapeutics. Proc Natl Acad Sci 109(40):16288–16293

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Marrache S, Dhar S (2013) Biodegradable synthetic high-density lipoprotein nanoparticles for atherosclerosis. Proc Natl Acad Sci 110(23):9445–9450

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Marrache S, Dhar S (2015) The energy blocker inside the power house: mitochondria targeted delivery of 3-bromopyruvate. Chem Sci 6(3):1832–1845

    Article  CAS  PubMed  Google Scholar 

  • Marrache S, Kumar Pathak R, Darley KL, Choi JH, Zaver D, Kolishetti N, Dhar S (2013) Nanocarriers for tracking and treating diseases. Curr Med Chem 20(28):3500–3514

    Article  CAS  PubMed  Google Scholar 

  • Marrache S, Pathak RK, Dhar S (2014) Detouring of cisplatin to access mitochondrial genome for overcoming resistance. Proc Natl Acad Sci 111(29):10444–10449

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Mathupala SP, Ko YH, Pedersen PL (2006) Hexokinase II: cancer’s double-edged sword acting as both facilitator and gatekeeper of malignancy when bound to mitochondria. Oncogene 25(34):4777–4786

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Matsuda S, Kitagishi Y, Kobayashi M (2013) Function and characteristics of PINK1 in mitochondria. Dig Oxid Med Cell Longev. doi:10.1155/2013/601587

    Google Scholar 

  • Maximo V, Lima J, Soares P, Sobrinho-Simoes M (2009) Mitochondria and cancer. Virchows Arch 454(5):481–495

    Article  CAS  PubMed  Google Scholar 

  • Milane L, Trivedi M, Singh A, Talekar M, Amiji M (2015) Mitochondrial biology, targets, and drug delivery. J Control Release 207:40–58

    Article  CAS  PubMed  Google Scholar 

  • Mizuno Y, Hattori N, Mori H, Suzuki T, Tanaka K (2001) Parkin and Parkinson’s disease. Curr Opin Neurol 14(4):477–482

    Google Scholar 

  • Mkandawire MM, Lakatos M, Springer A, Clemens A, Appelhans D, Krause-Buchholz U, Pompe W, Rodel G, Mkandawire M (2015) Induction of apoptosis in human cancer cells by targeting mitochondria with gold nanoparticles. Nanoscale 7(24):10634–10640

    Article  CAS  PubMed  Google Scholar 

  • Monici M (2005) Cell and tissue autofluorescence research and diagnostic applications. Biotechnol Annu Rev 11:227–256

    Article  CAS  PubMed  Google Scholar 

  • Mosiman VL, Patterson BK, Canterero L, Goolsby CL (1997) Reducing cellular autofluorescence in flow cytometry: an in situ method. Cytometry 30(3):151–156

    Article  CAS  PubMed  Google Scholar 

  • Nabi IR, Le PU (2003) Caveolae/raft-dependent endocytosis. J Cell Biol 161(4):673–677

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Nam HY, Kwon SM, Chung H, Lee S-Y, Kwon S-H, Jeon H, Kim Y, Park JH, Kim J, Her S, Oh Y-K, Kwon IC, Kim K, Jeong SY (2009) Cellular uptake mechanism and intracellular fate of hydrophobically modified glycol chitosan nanoparticles. J Control Release 135(3):259–267

    Article  CAS  PubMed  Google Scholar 

  • Nicholls DG, Ward MW (2000) Mitochondrial membrane potential and neuronal glutamate excitotoxicity: mortality and millivolts. Trends Neurosci 23(4):166–174

    Article  CAS  PubMed  Google Scholar 

  • Oh N, Park J-H (2014) Endocytosis and exocytosis of nanoparticles in mammalian cells. D Int J Nanomed. doi:10.2147/IJN.S26592

  • Oh J-M, Choi S-J, Kim S-T, Choy J-H (2006) Cellular uptake mechanism of an inorganic nanovehicle and its drug conjugates: enhanced efficacy due to clathrin-mediated endocytosis. Bioconjug Chem 17(6):1411–1417

    Article  CAS  PubMed  Google Scholar 

  • Pathak RK, Dhar S (2015) A nanoparticle cocktail: temporal release of predefined drug combinations. J Am Chem Soc 137(26):8324–8327

    Article  CAS  PubMed  Google Scholar 

  • Pathak RK, Marrache S, Harn DA, Dhar S (2014) Mito-DCA: a mitochondria targeted molecular scaffold for efficacious delivery of metabolic modulator dichloroacetate. ACS Chem Biol 9(5):1178–1187

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Pathak RK, Kolishetti N, Dhar S (2015) Targeted nanoparticles in mitochondrial medicine. WIREs Nanomed Nanobiotechnol 7(3):315–329

    Article  CAS  Google Scholar 

  • Peckys DB, de Jonge N (2011) Visualizing gold nanoparticle uptake in live cells with liquid scanning transmission electron microscopy. Nano Lett 11(4):1733–1738

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Pendergrass W, Wolf N, Poot M (2004) Efficacy of MitoTracker Green™ and CMXRosamine to measure changes in mitochondrial membrane potentials in living cells and tissues. Cytometry A 61(2):162–169

    Article  CAS  PubMed  Google Scholar 

  • Perry SW, Norman JP, Barbieri J, Brown EB, Gelbard HA (2011) Mitochondrial membrane potential probes and the proton gradient: a practical usage guide. Biotechniques 50(2):98–115

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Petersen CAH, Alikhani N, Behbahani H, Wiehager B, Pavlov PF, Alafuzoff I, Leinonen V, Ito A, Winblad B, Glaser E (2008) The amyloid β-peptide is imported into mitochondria via the TOM import machinery and localized to mitochondrial cristae. Proc Natl Acad Sci 105(35):13145–13150

    Article  Google Scholar 

  • Polyak K, Li Y, Zhu H, Lengauer C, Willson JKV, Markowitz SD, Trush MA, Kinzler KW, Vogelstein B (1998) Somatic mutations of the mitochondrial genome in human colorectal tumours. Nat Genet 20(3):291–293

    Article  CAS  PubMed  Google Scholar 

  • Poot M, Pierce RC (1999) Detection of apoptosis and changes in mitochondrial membrane potential with chloromethyl-X-rosamine. Cytometry 36(4):359–360

    Article  CAS  PubMed  Google Scholar 

  • Qaddoumi MG, Gukasyan HJ, Davda J, Labhasetwar V, Kim K-J, Lee V (2003) Clathrin and caveolin-1 expression in primary pigmented rabbit conjunctival epithelial cells: role in PLGA nanoparticle endocytosis. Mol Vis 9:559–568

    CAS  PubMed  Google Scholar 

  • Qu Q, Ma X, Zhao Y (2015) Targeted delivery of doxorubicin to mitochondria using mesoporous silica nanoparticle nanocarriers. Nanoscale 7(40):16677–16686

    Article  CAS  PubMed  Google Scholar 

  • Ratnam DV, Chandraiah G, Meena A, Ramarao P, Ravi Kumar M (2009) The co-encapsulated antioxidant nanoparticles of ellagic acid and coenzyme Q10 ameliorates hyperlipidemia in high fat diet fed rats. J Nanosci Nanotechnol 9(11):6741–6746

    Article  CAS  PubMed  Google Scholar 

  • Resch-Genger U, Grabolle M, Cavaliere-Jaricot S, Nitschke R, Nann T (2008) Quantum dots versus organic dyes as fluorescent labels. Nat Methods 5(9):763–775

    Article  CAS  PubMed  Google Scholar 

  • Rin Jean S, Tulumello DV, Wisnovsky SP, Lei EK, Pereira MP, Kelley SO (2014) Molecular vehicles for mitochondrial chemical biology and drug delivery. ACS Chem Biol 9(2):323–333

    Article  CAS  PubMed  Google Scholar 

  • Roberts CK, Sindhu KK (2009) Oxidative stress and metabolic syndrome. Dig Life Sci. doi:10.1016/j.lfs.2009.02.026

    Google Scholar 

  • Ross M, Kelso G, Blaikie F, James A, Cocheme H, Filipovska A, Da Ros T, Hurd T, Smith R, Murphy M (2005) Lipophilic triphenylphosphonium cations as tools in mitochondrial bioenergetics and free radical biology. Biochemistry 70(2):222–230

    CAS  PubMed  Google Scholar 

  • Sakhrani NM, Padh H (2013) Organelle targeting: third level of drug targeting. Drug Des Devel Ther 7:585–599

    CAS  PubMed  PubMed Central  Google Scholar 

  • Santucci R, Sinibaldi F, Polticelli F, Fiorucci L (2014) Role of cardiolipin in mitochondrial diseases and apoptosis. Curr Med Chem 21(23):2702–2714

    Article  CAS  PubMed  Google Scholar 

  • Scatena R (2012) Mitochondria and cancer: a growing role in apoptosis, cancer cell metabolism and dedifferentiation. Adv Exp Med Biol 942:287–308

    Article  CAS  PubMed  Google Scholar 

  • Schnell SA, Staines WA, Wessendorf MW (1999) Reduction of lipofuscin-like autofluorescence in fluorescently labeled tissue. J Histochem Cytochem 47(6):719–730

    Article  CAS  PubMed  Google Scholar 

  • Scorrano L, Petronilli V, Colonna R, Di Lisa F, Bernardi P (1999) Chloromethyltetramethylrosamine (Mitotracker OrangeTM) induces the mitochondrial permeability transition and inhibits respiratory complex I implication for the mechanism of cytochrome c release. J Biol Chem 274(35):24657–24663

    Article  CAS  PubMed  Google Scholar 

  • Sharma K (2015) Mitochondrial hormesis and diabetic complications. Diabetes 64(3):663–672

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Smith AM, Nie S (2009) Next-generation quantum dots. Nat Biotechnol 27(8):732–733

    Google Scholar 

  • Smith RA, Porteous CM, Gane AM, Murphy MP (2003) Delivery of bioactive molecules to mitochondria in vivo. Proc Natl Acad Sci 100(9):5407–5412

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Solazzo M, Fantappie O, Lasagna N, Sassoli C, Nosi D, Mazzanti R (2006) P-gp localization in mitochondria and its functional characterization in multiple drug-resistant cell lines. Exp Cell Res 312(20):4070–4078

    Article  CAS  PubMed  Google Scholar 

  • Stojanovski D, Bohnert M, Pfanner N, van der Laan M (2012) Mechanisms of protein sorting in mitochondria. Dig Cold Spring Harb Protoc. doi:10.1101/cshperspect.a011320

    Google Scholar 

  • Tatsuta T, Scharwey M, Langer T (2014) Mitochondrial lipid trafficking. Trends Cell Biol 24(1):44–52

    Article  CAS  PubMed  Google Scholar 

  • Ungewickell EJ, Hinrichsen L (2007) Endocytosis: clathrin-mediated membrane budding. Curr Opin Cell Biol 19(4):417–425

    Article  CAS  PubMed  Google Scholar 

  • van Gisbergen MW, Voets AM, Starmans MHW, de Coo IFM, Yadak R, Hoffmann RF, Boutros PC, Smeets HJM, Dubois L, Lambin P (2015) How do changes in the mtDNA and mitochondrial dysfunction influence cancer and cancer therapy? Challenges, opportunities and models. Mutat Res 764:16–30

    Article  CAS  Google Scholar 

  • Vasquez-Trincado C, Garcia-Carvajal I, Pennanen C, Parra V, Hill JA, Rothermel BA, Lavandero S (2016) Mitochondrial dynamics, mitophagy and cardiovascular disease. J Physiol 594(3):509–525

    Article  CAS  PubMed  Google Scholar 

  • Verma A, Uzun O, Hu Y, Hu Y, Han H-S, Watson N, Chen S, Irvine DJ, Stellacci F (2008) Surface-structure-regulated cell-membrane penetration by monolayer-protected nanoparticles. Nat Mater 7(7):588–595

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Verschoor ML, Ungard R, Harbottle A, Jakupciak JP, Parr RL, Singh G (2013) Mitochondria and cancer: past, present, and future. Biomed Res Int 2013:612369

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Vieira HL, Haouzi D, El Hamel C, Jacotot E, Belzacq AS, Brenner C, Kroemer G (2000) Permeabilization of the mitochondrial inner membrane during apoptosis: impact of the adenine nucleotide translocator. Cell Death Differ 7(12):1146–1154

    Article  CAS  PubMed  Google Scholar 

  • Voigt J, Christensen J, Shastri VP (2014) Differential uptake of nanoparticles by endothelial cells through polyelectrolytes with affinity for caveolae. Proc Natl Acad Sci 111(8):2942–2947

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Wallace DC (2012) Mitochondria and cancer. Nat Rev Cancer 12(10):685–698

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Walther DM, Rapaport D (2009) Biogenesis of mitochondrial outer membrane proteins. BBA-Mol Cell Res 1793(1):42–51

    CAS  Google Scholar 

  • Wang A, Melosh N (2012) Direct penetration of cell-penetrating peptides across lipid bilayers. Biophys J 102(3):487a

    Google Scholar 

  • Wang Z, Tiruppathi C, Minshall RD, Malik AB (2009) Size and dynamics of caveolae studied using nanoparticles in living endothelial cells. ACS Nano 3(12):4110–4116

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Weinberg SE, Chandel NS (2015) Targeting mitochondria metabolism for cancer therapy. Nat Chem Biol 11(1):9–15

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Weksler-Zangen S, Raz I, Lenzen S, Jorns A, Ehrenfeld S, Amir G, Oprescu A, Yagil Y, Yagil C, Zangen DH, Kaiser N (2008) Impaired glucose-stimulated insulin secretion is coupled with exocrine pancreatic lesions in the Cohen diabetic rat. Diabetes 57(2):279–287

    Article  CAS  PubMed  Google Scholar 

  • Wen R, Banik B, Pathak RK, Kumar A, Kolishetti N, Dhar S (2016) Nanotechnology inspired tools for mitochondrial dysfunction related diseases. Adv Drug Deliv Rev 99(A): 52–69

    Google Scholar 

  • White J, Amos W, Fordham M (1987) An evaluation of confocal versus conventional imaging of biological structures by fluorescence light microscopy. J Cell Biol 105(1):41–48

    Article  CAS  PubMed  Google Scholar 

  • Wickramasekera NT, Das GM (2014) Tumor suppressor p53 and estrogen receptors in nuclear–mitochondrial communication. Mitochondrion 16:26–37

    Article  CAS  PubMed  Google Scholar 

  • Yamada Y, Harashima H (2013) Enhancement in selective mitochondrial association by direct modification of a mitochondrial targeting signal peptide on a liposomal based nanocarrier. Mitochondrion 13(5):526–532

    Article  CAS  PubMed  Google Scholar 

  • Yamada Y, Akita H, Kamiya H, Kogure K, Yamamoto T, Shinohara Y, Yamashita K, Kobayashi H, Kikuchi H, Harashima H (2008) MITO-Porter: A liposome-based carrier system for delivery of macromolecules into mitochondria via membrane fusion. BBA Biomembranes 1778(2):423–432

    Article  CAS  PubMed  Google Scholar 

  • Yamada Y, Fukuda Y, Harashima H (2015a) An analysis of membrane fusion between mitochondrial double membranes and MITO-Porter, mitochondrial fusogenic vesicles. Mitochondrion 24:50–55

    Article  CAS  PubMed  Google Scholar 

  • Yamada Y, Nakamura K, Abe J, Hyodo M, Haga S, Ozaki M, Harashima H (2015b) Mitochondrial delivery of Coenzyme Qvia systemic administration using a MITO-Porter prevents ischemia/reperfusion injury in the mouse liver. J Control Release 213:86–95

    Article  CAS  PubMed  Google Scholar 

  • Yang S-T, Cao L, Luo PG, Lu F, Wang X, Wang H, Meziani MJ, Liu Y, Qi G, Sun Y-P (2009) Carbon dots for optical imaging in vivo. J Am Chem Soc 131(32):11308–11309

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Yousif LF, Stewart KM, Kelley SO (2009) Targeting mitochondria with organelle-specific compounds: strategies and applications. ChemBioChem 10(12):1939–1950

    Article  CAS  PubMed  Google Scholar 

  • Zhang E, Zhang C, Su Y, Cheng T, Shi C (2011) Newly developed strategies for multifunctional mitochondria-targeted agents in cancer therapy. Drug Discov Today 16(3–4):140–146

    Article  CAS  PubMed  Google Scholar 

  • Zhang Y, Shen Y, Teng X, Yan M, Bi H, Morais PC (2015) Mitochondria-targeting nanoplatform with fluorescent carbon dots for long time imaging and magnetic field-enhanced cellular uptake. ACS Appl Mater Interfaces 7(19):10201–10212

    Article  CAS  PubMed  Google Scholar 

  • Zhou F, Xing D, Wu B, Wu S, Ou Z, Chen WR (2010) New insights of transmembranal mechanism and subcellular localization of noncovalently modified single-walled carbon nanotubes. Nano Lett 10(5):1677–1681

    Article  CAS  PubMed  Google Scholar 

Download references

Acknowledgements

We are thankful to the Department of Defense for a Prostate Cancer Idea award (W81XWH-12-1-0406); American Heart Association for a National Scientist Award (14SDG18690009); National Heart, Lung, and Blood Institute of National Institutes of Health (NIH) R56 high priority bridge award (Award Number. R56HL121392); National Institute of Neurological Disorders and Stroke of NIH R01NS093314 award, Georgia Research Alliance, and Sylvester Comprehensive Cancer Center for providing financial supports to conduct research in our lab in the area of nanomedicine.

Author information

Authors and Affiliations

  1. NanoTherapeutics Research Laboratory, Department of Biochemistry and Molecular Biology, Sylvester Comprehensive Cancer Center, Miller School of Medicine, University of Miami, Miami, FL, 33136, USA

    Ru Wen, Afoma C. Umeano & Shanta Dhar

Authors
  1. Ru Wen
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Afoma C. Umeano
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Shanta Dhar
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Shanta Dhar .

Editor information

Editors and Affiliations

  1. Biomolecular and Chemical Engineering, Vanderbilt University Biomolecular and Chemical Engineering, Nashville, Tennessee, USA

    Aleš Prokop

  2. Pharmaceutical Sciences, Midwestern University Pharmaceutical Sciences, GLENDALE, Arizona, USA

    Volkmar Weissig

Rights and permissions

Reprints and permissions

Copyright information

© 2016 Springer International Publishing Switzerland

About this chapter

Cite this chapter

Wen, R., Umeano, A.C., Dhar, S. (2016). Accessing Mitochondrial Targets Using NanoCargos. In: Prokop, A., Weissig, V. (eds) Intracellular Delivery III. Fundamental Biomedical Technologies. Springer, Cham. https://doi.org/10.1007/978-3-319-43525-1_9

Download citation

Publish with us

Policies and ethics

Search

Navigation