Autophagy and lysosomal dysfunction as emerging mechanisms of nanomaterial toxicity

Li N, Xia T, Nel AE: The role of oxidative stress in ambient particulate matter-induced lung diseases and its implications in the toxicity of engineered nanoparticles. Free Radic Biol Med 2008, 44: 1689–1699. 10.1016/j.freeradbiomed.2008.01.028

Stern ST, Johnson DN: Role for nanomaterial-autophagy interaction in neurodegenerative disease. Autophagy 2008, 4: 1097–1100.

Klionsky DJ: Autophagy: from phenomenology to molecular understanding in less than a decade. Nat Rev Mol Cell Biol 2007, 8: 931–937. 10.1038/nrm2245

De Duve C, De Barsy T, Poole B, Trouet A, Tulkens P, Van Hoof F: Commentary. Lysosomotropic agents. Biochem Pharmacol 1974, 23: 2495–2531. 10.1016/0006-2952(74)90174-9

Hillaireau H, Couvreur P: Nanocarriers' entry into the cell: relevance to drug delivery. Cell Mol Life Sci 2009, 66: 2873–2896. 10.1007/s00018-009-0053-z

Sahay G, Alakhova DY, Kabanov AV: Endocytosis of nanomedicines. J Control Release 2010, 145: 182–195. 10.1016/j.jconrel.2010.01.036

Zaki NM, Tirelli N: Gateways for the intracellular access of nanocarriers: a review of receptor-mediated endocytosis mechanisms and of strategies in receptor targeting. Expert Opin Drug Deliv 2010, 7: 895–913. 10.1517/17425247.2010.501792

Brandenberger C, Clift MJ, Vanhecke D, Muhlfeld C, Stone V, Gehr P, Rothen-Rutishauser B: Intracellular imaging of nanoparticles: is it an elemental mistake to believe what you see? Particle and fibre toxicology 2010, 7: 15. 10.1186/1743-8977-7-15

Seib FP, Jones AT, Duncan R: Establishment of subcellular fractionation techniques to monitor the intracellular fate of polymer therapeutics I. Differential centrifugation fractionation B16F10 cells and use to study the intracellular fate of HPMA copolymer - doxorubicin. J Drug Target 2006, 14: 375–390. 10.1080/10611860600833955

Vercauteren D, Vandenbroucke RE, Jones AT, Rejman J, Demeester J, De Smedt SC, Sanders NN, Braeckmans K: The use of inhibitors to study endocytic pathways of gene carriers: optimization and pitfalls. Mol Ther 2010, 18: 561–569. 10.1038/mt.2009.281

Manunta M, Izzo L, Duncan R, Jones AT: Establishment of subcellular fractionation techniques to monitor the intracellular fate of polymer therapeutics II. Identification of endosomal and lysosomal compartments in HepG2 cells combining single-step subcellular fractionation with fluorescent imaging. J Drug Target 2007, 15: 37–50. 10.1080/10611860601010330

Conner SD, Schmid SL: Regulated portals of entry into the cell. Nature 2003, 422: 37–44. 10.1038/nature01451

Aderem A, Underhill DM: Mechanisms of phagocytosis in macrophages. Annu Rev Immunol 1999, 17: 593–623. 10.1146/annurev.immunol.17.1.593

Immordino ML, Dosio F, Cattel L: Stealth liposomes: review of the basic science, rationale, and clinical applications, existing and potential. Int J Nanomedicine 2006, 1: 297–315. 10.2217/17435889.1.3.297

Vonarbourg A, Passirani C, Saulnier P, Benoit JP: Parameters influencing the stealthiness of colloidal drug delivery systems. Biomaterials 2006, 27: 4356–4373. 10.1016/j.biomaterials.2006.03.039

Bareford LM, Swaan PW: Endocytic mechanisms for targeted drug delivery. Adv Drug Deliv Rev 2007, 59: 748–758. 10.1016/j.addr.2007.06.008

Marsh M, Helenius A: Virus entry: open sesame. Cell 2006, 124: 729–740. 10.1016/j.cell.2006.02.007

Pelkmans L, Kartenbeck J, Helenius A: Caveolar endocytosis of simian virus 40 reveals a new two-step vesicular-transport pathway to the ER. Nat Cell Biol 2001, 3: 473–483. 10.1038/35074539

Dauty E, Remy JS, Zuber G, Behr JP: Intracellular delivery of nanometric DNA particles via the folate receptor. Bioconjug Chem 2002, 13: 831–839. 10.1021/bc0255182

Thurn KT, Arora H, Paunesku T, Wu A, Brown EM, Doty C, Kremer J, Woloschak G: Endocytosis of titanium dioxide nanoparticles in prostate cancer PC-3 M cells. Nanomedicine 2011, 7: 123–130. 10.1016/j.nano.2010.09.004

He C, Klionsky DJ: Regulation mechanisms and signaling pathways of autophagy. Annu Rev Genet 2009, 43: 67–93. 10.1146/annurev-genet-102808-114910

Barth S, Glick D, Macleod KF: Autophagy: assays and artifacts. J Pathol 2010, 221: 117–124. 10.1002/path.2694

Komatsu M, Ichimura Y: Selective autophagy regulates various cellular functions. Genes Cells 2010, 15: 923–933. 10.1111/j.1365-2443.2010.01433.x

Ichimura Y, Komatsu M: Selective degradation of p62 by autophagy. Semin Immunopathol 2010, 32: 431–436. 10.1007/s00281-010-0220-1

Ni HM, Bockus A, Wozniak AL, Jones K, Weinman S, Yin XM, Ding WX: Dissecting the dynamic turnover of GFP-LC3 in the autolysosome. Autophagy 2011, 7: 188–204. 10.4161/auto.7.2.14181

Herd HL, Malugin A, Ghandehari H: Silica nanoconstruct cellular toleration threshold in vitro. J Control Release 2011, 153: 40–48. 10.1016/j.jconrel.2011.02.017

Li H, Li Y, Jiao J, Hu HM: Alpha-alumina nanoparticles induce efficient autophagy-dependent cross-presentation and potent antitumour response. Nat Nanotechnol 2011, 6: 645–650. 10.1038/nnano.2011.153

Monick MM, Powers LS, Walters K, Lovan N, Zhang M, Gerke A, Hansdottir S, Hunninghake GW: Identification of an autophagy defect in smokers' alveolar macrophages. J Immunol 2010, 185: 5425–5435. 10.4049/jimmunol.1001603

Seleverstov O, Zabirnyk O, Zscharnack M, Bulavina L, Nowicki M, Heinrich JM, Yezhelyev M, Emmrich F, O'Regan R, Bader A: Quantum dots for human mesenchymal stem cells labeling. A size-dependent autophagy activation. Nano Lett 2006, 6: 2826–2832.

Yokoyama T, Tam J, Kuroda S, Scott AW, Aaron J, Larson T, Shanker M, Correa AM, Kondo S, Roth JA, Sokolov K, Ramesh R: EGFR-targeted hybrid plasmonic magnetic nanoparticles synergistically induce autophagy and apoptosis in non-small cell lung cancer cells. PLoS One 2011, 6: e25507. 10.1371/journal.pone.0025507

Johnson-Lyles DN, Peifley K, Lockett S, Neun BW, Hansen M, Clogston J, Stern ST, McNeil SE: Fullerenol cytotoxicity in kidney cells is associated with cytoskeleton disruption, autophagic vacuole accumulation, and mitochondrial dysfunction. Toxicol Appl Pharmacol 2010, 248: 249–258. 10.1016/j.taap.2010.08.008

Ravikumar B, Sarkar S, Davies JE, Futter M, Garcia-Arencibia M, Green-Thompson ZW, Jimenez-Sanchez M, Korolchuk VI, Lichtenberg M, Luo S, Massey DC, Menzies FM, Moreau K, Narayanan U, Renna M, Siddiqi FH, Underwood BR, Winslow AR, Rubinsztein DC: Regulation of mammalian autophagy in physiology and pathophysiology. Physiol Rev 2010, 90: 1383–1435. 10.1152/physrev.00030.2009

Kroemer G, Jaattela M: Lysosomes and autophagy in cell death control. Nat Rev Cancer 2005, 5: 886–897. 10.1038/nrc1738

Sohaebuddin SK, Thevenot PT, Baker D, Eaton JW, Tang L: Nanomaterial cytotoxicity is composition, size, and cell type dependent. Particle and fibre toxicology 2010, 7: 22. 10.1186/1743-8977-7-22

Tedesco S, Doyle H, Blasco J, Redmond G, Sheehan D: Oxidative stress and toxicity of gold nanoparticles in Mytilus edulis. Aquat Toxicol 2010, 100: 178–186. 10.1016/j.aquatox.2010.03.001

Vevers WF, Jha AN: Genotoxic and cytotoxic potential of titanium dioxide (TiO2) nanoparticles on fish cells in vitro. Ecotoxicology 2008, 17: 410–420. 10.1007/s10646-008-0226-9

Thomas TP, Majoros I, Kotlyar A, Mullen D, Holl MM, Baker JR: Cationic poly(amidoamine) dendrimer induces lysosomal apoptotic pathway at therapeutically relevant concentrations. Biomacromolecules 2009, 10: 3207–3214. 10.1021/bm900683r

Koehler A, Marx U, Broeg K, Bahns S, Bressling J: Effects of nanoparticles in Mytilus edulis gills and hepatopancreas - a new threat to marine life? Mar Environ Res 2008, 66: 12–14. 10.1016/j.marenvres.2008.02.009

Jin CY, Zhu BS, Wang XF, Lu QH: Cytotoxicity of titanium dioxide nanoparticles in mouse fibroblast cells. Chem Res Toxicol 2008, 21: 1871–1877. 10.1021/tx800179f

Ringwood AH, McCarthy M, Bates TC, Carroll DL: The effects of silver nanoparticles on oyster embryos. Mar Environ Res 2010,69(Suppl):S49–51.

Ringwood AH, Levi-Polyachenko N, Carroll DL: Fullerene exposures with oysters: embryonic, adult, and cellular responses. Environ Sci Technol 2009, 43: 7136–7141. 10.1021/es900621j

Allison AC, Harington JS, Birbeck M: An examination of the cytotoxic effects of silica on macrophages. J Exp Med 1966, 124: 141–154. 10.1084/jem.124.2.141

Bendele A, Seely J, Richey C, Sennello G, Shopp G: Short communication: renal tubular vacuolation in animals treated with polyethylene-glycol-conjugated proteins. Toxicol Sci 1998, 42: 152–157. 10.1093/toxsci/42.2.152

Hussain S, Thomassen LC, Ferecatu I, Borot MC, Andreau K, Martens JA, Fleury J, Baeza-Squiban A, Marano F, Boland S: Carbon black and titanium dioxide nanoparticles elicit distinct apoptotic pathways in bronchial epithelial cells. Particle and fibre toxicology 2010, 7: 10. 10.1186/1743-8977-7-10

Chen HH, Yu C, Ueng TH, Chen S, Chen BJ, Huang KJ, Chiang LY: Acute and subacute toxicity study of water-soluble polyalkylsulfonated C60 in rats. Toxicol Pathol 1998, 26: 143–151. 10.1177/019262339802600117

Cho WS, Duffin R, Howie SE, Scotton CJ, Wallace WA, Macnee W, Bradley M, Megson IL, Donaldson K: Progressive severe lung injury by zinc oxide nanoparticles; the role of Zn2+ dissolution inside lysosomes. Particle and fibre toxicology 2011, 8: 27. 10.1186/1743-8977-8-27

Hamilton RF, Wu N, Porter D, Buford M, Wolfarth M, Holian A: Particle length-dependent titanium dioxide nanomaterials toxicity and bioactivity. Particle and fibre toxicology 2009, 6: 35. 10.1186/1743-8977-6-35

Lunov O, Syrovets T, Loos C, Nienhaus GU, Mailander V, Landfester K, Rouis M, Simmet T: Amino-Functionalized Polystyrene Nanoparticles Activate the NLRP3 Inflammasome in Human Macrophages. ACS Nano 2011, 5: 9648–9657. 10.1021/nn203596e

Futerman AH, van Meer G: The cell biology of lysosomal storage disorders. Nat Rev Mol Cell Biol 2004, 5: 554–565. 10.1038/nrm1423

Aldenhoven M, Sakkers RJ, Boelens J, de Koning TJ, Wulffraat NM: Musculoskeletal manifestations of lysosomal storage disorders. Ann Rheum Dis 2009, 68: 1659–1665. 10.1136/ard.2008.095315

Bellettato CM, Scarpa M: Pathophysiology of neuropathic lysosomal storage disorders. J Inherit Metab Dis 2010, 33: 347–362. 10.1007/s10545-010-9075-9

Settembre C, Fraldi A, Jahreiss L, Spampanato C, Venturi C, Medina D, de Pablo R, Tacchetti C, Rubinsztein DC, Ballabio A: A block of autophagy in lysosomal storage disorders. Hum Mol Genet 2008, 17: 119–129.

Kovacs AL, Seglen PO: Inhibition of hepatocytic protein degradation by inducers of autophagosome accumulation. Acta Biol Med Ger 1982, 41: 125–130.

Shcharbin D, Jokiel M, Klajnert B, Bryszewska M: Effect of dendrimers on pure acetylcholinesterase activity and structure. Bioelectrochemistry 2006, 68: 56–59. 10.1016/j.bioelechem.2005.04.001

Ueng TH, Kang JJ, Wang HW, Cheng YW, Chiang LY: Suppression of microsomal cytochrome P450-dependent monooxygenases and mitochondrial oxidative phosphorylation by fullerenol, a polyhydroxylated fullerene C60. Toxicol Lett 1997, 93: 29–37. 10.1016/S0378-4274(97)00071-4

Xia T, Kovochich M, Liong M, Zink JI, Nel AE: Cationic polystyrene nanosphere toxicity depends on cell-specific endocytic and mitochondrial injury pathways. ACS Nano 2008, 2: 85–96. 10.1021/nn700256c

Thibodeau MS, Giardina C, Knecht DA, Helble J, Hubbard AK: Silica-induced apoptosis in mouse alveolar macrophages is initiated by lysosomal enzyme activity. Toxicol Sci 2004, 80: 34–48. 10.1093/toxsci/kfh121

Franchi L, Eigenbrod T, Munoz-Planillo R, Nunez G: The inflammasome: a caspase-1-activation platform that regulates immune responses and disease pathogenesis. Nat Immunol 2009, 10: 241–247.

Meunier E, Coste A, Olagnier D, Authier H, Lefevre L, Dardenne C, Bernad J, Beraud M, Flahaut E, Pipy B: Double-walled carbon nanotubes trigger IL-1beta release in human monocytes through Nlrp3 inflammasome activation. Nanomedicine 2011. [epub ahead of print]

Nakashima S, Hiraku Y, Tada-Oikawa S, Hishita T, Gabazza EC, Tamaki S, Imoto I, Adachi Y, Kawanishi S: Vacuolar H + −ATPase inhibitor induces apoptosis via lysosomal dysfunction in the human gastric cancer cell line MKN-1. J Biochem 2003, 134: 359–364. 10.1093/jb/mvg153

Chen ZH, Lam HC, Jin Y, Kim HP, Cao J, Lee SJ, Ifedigbo E, Parameswaran H, Ryter SW, Choi AM: Autophagy protein microtubule-associated protein 1 light chain-3B (LC3B) activates extrinsic apoptosis during cigarette smoke-induced emphysema. Proc Natl Acad Sci USA 2010, 107: 18880–18885. 10.1073/pnas.1005574107

Yousefi S, Perozzo R, Schmid I, Ziemiecki A, Schaffner T, Scapozza L, Brunner T, Simon HU: Calpain-mediated cleavage of Atg5 switches autophagy to apoptosis. Nat Cell Biol 2006, 8: 1124–1132. 10.1038/ncb1482

Wei Y, Sinha S, Levine B: Dual role of JNK1-mediated phosphorylation of Bcl-2 in autophagy and apoptosis regulation. Autophagy 2008, 4: 949–951.

Wu YC, Wu WK, Li Y, Yu L, Li ZJ, Wong CC, Li HT, Sung JJ, Cho CH: Inhibition of macroautophagy by bafilomycin A1 lowers proliferation and induces apoptosis in colon cancer cells. Biochem Biophys Res Commun 2009, 382: 451–456. 10.1016/j.bbrc.2009.03.051

Qu X, Yu J, Bhagat G, Furuya N, Hibshoosh H, Troxel A, Rosen J, Eskelinen EL, Mizushima N, Ohsumi Y, Cattoretti G, Levine B: Promotion of tumorigenesis by heterozygous disruption of the beclin 1 autophagy gene. J Clin Invest 2003, 112: 1809–1820.

Livesey KM, Tang D, Zeh HJ, Lotze MT: Autophagy inhibition in combination cancer treatment. Curr Opin Investig Drugs 2009, 10: 1269–1279.

Brest P, Corcelle EA, Cesaro A, Chargui A, Belaid A, Klionsky DJ, Vouret-Craviari V, Hebuterne X, Hofman P, Mograbi B: Autophagy and Crohn's disease: at the crossroads of infection, inflammation, immunity, and cancer. Curr Mol Med 2010, 10: 486–502. 10.2174/156652410791608252

Moreira PI, Santos RX, Zhu X, Lee HG, Smith MA, Casadesus G, Perry G: Autophagy in Alzheimer's disease. Expert Rev Neurother 2010, 10: 1209–1218. 10.1586/ern.10.84

Pan T, Kondo S, Le W, Jankovic J: The role of autophagy-lysosome pathway in neurodegeneration associated with Parkinson's disease. Brain 2008, 131: 1969–1978. 10.1093/brain/awm318

Gazouli M, Pachoula I, Panayotou I, Mantzaris G, Chrousos G, Anagnou NP, Roma-Giannikou E: NOD2/CARD15, ATG16L1 and IL23R gene polymorphisms and childhood-onset of Crohn's disease. World J Gastroenterol 2010, 16: 1753–1758. 10.3748/wjg.v16.i14.1753

Geisler S, Holmstrom KM, Treis A, Skujat D, Weber SS, Fiesel FC, Kahle PJ, Springer W: The PINK1/Parkin-mediated mitophagy is compromised by PD-associated mutations. Autophagy 2010, 6: 871–878. 10.4161/auto.6.7.13286

Lapaquette P, Darfeuille-Michaud A: Abnormalities in the handling of intracellular bacteria in Crohn's disease. J Clin Gastroenterol 2010,44(Suppl 1):S26–29.

Pickford F, Masliah E, Britschgi M, Lucin K, Narasimhan R, Jaeger PA, Small S, Spencer B, Rockenstein E, Levine B, Wyss-Coray T: The autophagy-related protein beclin 1 shows reduced expression in early Alzheimer disease and regulates amyloid beta accumulation in mice. J Clin Invest 2008, 118: 2190–2199.

Afeseh Ngwa H, Kanthasamy A, Gu Y, Fang N, Anantharam V, Kanthasamy AG: Manganese nanoparticle activates mitochondrial dependent apoptotic signaling and autophagy in dopaminergic neuronal cells. Toxicol Appl Pharmacol 2011, 256: 227–240. 10.1016/j.taap.2011.07.018

Chen Y, Yang L, Feng C, Wen LP: Nano neodymium oxide induces massive vacuolization and autophagic cell death in non-small cell lung cancer NCI-H460 cells. Biochem Biophys Res Commun 2005, 337: 52–60. 10.1016/j.bbrc.2005.09.018

Lee CM, Huang ST, Huang SH, Lin HW, Tsai HP, Wu JY, Lin CM, Chen CT: C(60) fullerene-pentoxifylline dyad nanoparticles enhance autophagy to avoid cytotoxic effects caused by the beta-amyloid peptide. Nanomedicine 2011, 7: 107–114. 10.1016/j.nano.2010.06.009

Ma X, Wu Y, Jin S, Tian Y, Zhang X, Zhao Y, Liang XJ Yu L: Gold Nanoparticles Induce Autophagosome Accumulation through Size-Dependent Nanoparticle Uptake and Lysosome Impairment. ACS Nano 2011, 5: 8629–8639. 10.1021/nn202155y

Khan MI, Mohammad A, Patil G, Naqvi SA, Chauhan LK, Ahmad I: Induction of ROS, mitochondrial damage and autophagy in lung epithelial cancer cells by iron oxide nanoparticles. Biomaterials 2012, 33: 1477–1488. 10.1016/j.biomaterials.2011.10.080

Eidi H, Joubert O, Nemos C, Grandemange S, Mograbi B, Foliguet B, Tournebize J, Maincent P, Le Faou A, Aboukhamis I, Rihn BH: Drug delivery by polymeric nanoparticles induces autophagy in macrophages. Int J Pharm 2012, 422: 495–503. 10.1016/j.ijpharm.2011.11.020

Zhang Y, Yu C, Huang G, Wang C, Wen L: Nano rare-earth oxides induced size-dependent vacuolization: an independent pathway from autophagy. Int J Nanomedicine 2010, 5: 601–609.

Wei P, Zhang L, Lu Y, Man N, Wen L: C60(Nd) nanoparticles enhance chemotherapeutic susceptibility of cancer cells by modulation of autophagy. Nanotechnology 2010, 21: 495101. 10.1088/0957-4484/21/49/495101

Stern ST, Zolnik BS, McLeland CB, Clogston J, Zheng J, McNeil SE: Induction of autophagy in porcine kidney cells by quantum dots: a common cellular response to nanomaterials? Toxicol Sci 2008, 106: 140–152. 10.1093/toxsci/kfn137

Li C, Liu H, Sun Y, Wang H, Guo F, Rao S, Deng J, Zhang Y, Miao Y, Guo C, Meng J, Chen X, Li L, Li D, Xu H, Wang H, Li B, Jiang C: PAMAM nanoparticles promote acute lung injury by inducing autophagic cell death through the Akt-TSC2-mTOR signaling pathway. J Mol Cell Biol 2009, 1: 37–45. 10.1093/jmcb/mjp002

Harhaji L, Isakovic A, Raicevic N, Markovic Z, Todorovic-Markovic B, Nikolic N, Vranjes-Djuric S, Markovic I, Trajkovic V: Multiple mechanisms underlying the anticancer action of nanocrystalline fullerene. Eur J Pharmacol 2007, 568: 89–98. 10.1016/j.ejphar.2007.04.041

Wu YN, Yang LX, Shi XY, Li IC, Biazik JM, Ratinac KR, Chen DH, Thordarson P, Shieh DB, Braet F: The selective growth inhibition of oral cancer by iron core-gold shell nanoparticles through mitochondria-mediated autophagy. Biomaterials 2011, 32: 4565–4573. 10.1016/j.biomaterials.2011.03.006

Yu JX, Li TH: Distinct biological effects of different nanoparticles commonly used in cosmetics and medicine coatings. Cell Biosci 2011, 1: 19. 10.1186/2045-3701-1-19

Liu HL, Zhang YL, Yang N, Zhang YX, Liu XQ, Li CG, Zhao Y, Wang YG, Zhang GG, Yang P, Guo F, Sun Y, Jiang CY: A functionalized single-walled carbon nanotube-induced autophagic cell death in human lung cells through Akt-TSC2-mTOR signaling. Cell Death Dis 2011, 2: e159. 10.1038/cddis.2011.27

Li JJ, Hartono D, Ong CN, Bay BH, Yung LY: Autophagy and oxidative stress associated with gold nanoparticles. Biomaterials 2010, 31: 5996–6003. 10.1016/j.biomaterials.2010.04.014

Zhang Q, Yang W, Man N, Zheng F, Shen Y, Sun K, Li Y, Wen LP: Autophagy-mediated chemosensitization in cancer cells by fullerene C60 nanocrystal. Autophagy 2009, 5: 1107–1117. 10.4161/auto.5.8.9842

Yu L, Lu Y, Man N, Yu SH, Wen LP: Rare earth oxide nanocrystals induce autophagy in HeLa cells. Small 2009, 5: 2784–2787. 10.1002/smll.200901714

Yamawaki H, Iwai N: Cytotoxicity of water-soluble fullerene in vascular endothelial cells. Am J Physiol Cell Physiol 2006, 290: C1495–1502. 10.1152/ajpcell.00481.2005

Yoshikawa Y, Ogawa M, Hain T, Yoshida M, Fukumatsu M, Kim M, Mimuro H, Nakagawa I, Yanagawa T, Ishii T, Kakizuka A, Sztul E, Chakraborty T, Sasakawa C: Listeria monocytogenes ActA-mediated escape from autophagic recognition. Nat Cell Biol 2009, 11: 1233–1240. 10.1038/ncb1967

Zheng YT, Shahnazari S, Brech A, Lamark T, Johansen T, Brumell JH: The adaptor protein p62/SQSTM1 targets invading bacteria to the autophagy pathway. J Immunol 2009, 183: 5909–5916. 10.4049/jimmunol.0900441

Calzolai L, Franchini F, Gilliland D, Rossi F: Protein–nanoparticle interaction: identification of the ubiquitin–gold nanoparticle interaction site. Nano Lett 2010, 10: 3101–3105. 10.1021/nl101746v

Chen M, von Mikecz A: Formation of nucleoplasmic protein aggregates impairs nuclear function in response to SiO2 nanoparticles. Exp Cell Res 2005, 305: 51–62. 10.1016/j.yexcr.2004.12.021

Shrivas K, Wu HF: Modified silver nanoparticle as a hydrophobic affinity probe for analysis of peptides and proteins in biological samples by using liquid-liquid microextraction coupled to AP-MALDI-ion trap and MALDI-TOF mass spectrometry. Anal Chem 2008, 80: 2583–2589. 10.1021/ac702309w

Wu HF, Kailasa SK, Shastri L: Electrostatically self-assembled azides on zinc sulfide nanoparticles as multifunctional nanoprobes for peptide and protein analysis in MALDI-TOF MS. Talanta 2010, 82: 540–547. 10.1016/j.talanta.2010.05.026

Anderson N, Borlak J: Drug-induced phospholipidosis. FEBS Lett 2006, 580: 5533–5540. 10.1016/j.febslet.2006.08.061

Shi CS, Shenderov K, Huang NN, Kabat J, Abu-Asab M, Fitzgerald KA, Sher A, Kehrl JH: Activation of autophagy by inflammatory signals limits IL-1beta production by targeting ubiquitinated inflammasomes for destruction. Nat Immunol 2012, 13: 255–263. 10.1038/ni.2215

Kim I, Lemasters JJ: Mitophagy Selectively Degrades Individual Damaged Mitochondria After Photoirradiation. Antioxid Redox Signal 2011, 14: 1919–1928. 10.1089/ars.2010.3768

Elmore SP, Qian T, Grissom SF, Lemasters JJ: The mitochondrial permeability transition initiates autophagy in rat hepatocytes. FASEB J 2001, 15: 2286–2287.

Degtyarev M, De Maziere A, Orr C, Lin J, Lee BB, Tien JY, Prior WW, van Dijk S, Wu H, Gray DC, Davis DP, Stern HM, Murray LJ, Hoeflich KP, Klumperman J, Friedman LS, Lin K: Akt inhibition promotes autophagy and sensitizes PTEN-null tumors to lysosomotropic agents. J Cell Biol 2008, 183: 101–116. 10.1083/jcb.200801099

Boya P, Gonzalez-Polo RA, Casares N, Perfettini JL, Dessen P, Larochette N, Metivier D, Meley D, Souquere S, Yoshimori T, Pierron G, Codogno P, Kroemer G: Inhibition of macroautophagy triggers apoptosis. Mol Cell Biol 2005, 25: 1025–1040. 10.1128/MCB.25.3.1025-1040.2005

Yamawaki H, Iwai N: Mechanisms underlying nano-sized air-pollution-mediated progression of atherosclerosis: carbon black causes cytotoxic injury/inflammation and inhibits cell growth in vascular endothelial cells. Circ J 2006, 70: 129–140. 10.1253/circj.70.129

Oberdörster G, Ferin J, Soderholm S, Gelein R, Cox C, Baggs R, Morrow PE: Increased Pulmonary Toxicity of Inhaled Ultrafine Particles: Due to Lung Overload Alone? Ann Occup Hyg 1994, 38: 295–302.

Levine B: Eating oneself and uninvited guests: autophagy-related pathways in cellular defense. Cell 2005, 120: 159–162.

Korolchuk VI, Mansilla A, Menzies FM, Rubinsztein DC: Autophagy inhibition compromises degradation of ubiquitin-proteasome pathway substrates. Mol Cell 2009, 33: 517–527. 10.1016/j.molcel.2009.01.021

Berndt C, Kurz T, Selenius M, Fernandes AP, Edgren MR, Brunk UT: Chelation of lysosomal iron protects against ionizing radiation. Biochem J 2010, 432: 295–301. 10.1042/BJ20100996

Huynh C, Roth D, Ward DM, Kaplan J, Andrews NW: Defective lysosomal exocytosis and plasma membrane repair in Chediak-Higashi/beige cells. Proc Natl Acad Sci USA 2004, 101: 16795–16800. 10.1073/pnas.0405905101

Montgomery RR, Webster P, Mellman I: Accumulation of indigestible substances reduces fusion competence of macrophage lysosomes. J Immunol 1991, 147: 3087–3095.

Blankson H, Holen I, Seglen PO: Disruption of the cytokeratin cytoskeleton and inhibition of hepatocytic autophagy by okadaic acid. Exp Cell Res 1995, 218: 522–530. 10.1006/excr.1995.1187

Seglen PO, Brinchmann MF: Purification of autophagosomes from rat hepatocytes. Autophagy 2010, 6: 542–547. 10.4161/auto.6.4.11272

Kochl R, Hu XW, Chan EY, Tooze SA: Microtubules facilitate autophagosome formation and fusion of autophagosomes with endosomes. Traffic (Copenhagen, Denmark) 2006, 7: 129–145. 10.1111/j.1600-0854.2005.00368.x

Xie R, Nguyen S, McKeehan WL, Liu L: Acetylated microtubules are required for fusion of autophagosomes with lysosomes. BMC Cell Biol 2010, 11: 89. 10.1186/1471-2121-11-89

Lee JY, Koga H, Kawaguchi Y, Tang W, Wong E, Gao YS, Pandey UB, Kaushik S, Tresse E, Lu J, Taylor JP, Cuervo AM, Yao TP: HDAC6 controls autophagosome maturation essential for ubiquitin-selective quality-control autophagy. EMBO J 2010, 29: 969–980. 10.1038/emboj.2009.405

Ehrenberg M, McGrath JL: Binding between particles and proteins in extracts: implications for microrheology and toxicity. Acta Biomater 2005, 1: 305–315. 10.1016/j.actbio.2005.02.002

Ruenraroengsak P, Florence AT: Biphasic interactions between a cationic dendrimer and actin. J Drug Target 2010, 18: 803–811. 10.3109/1061186X.2010.521159

Walker VG, Li Z, Hulderman T, Schwegler-Berry D, Kashon ML, Simeonova PP: Potential in vitro effects of carbon nanotubes on human aortic endothelial cells. Toxicol Appl Pharmacol 2009, 236: 319–328. 10.1016/j.taap.2009.02.018

Mironava T, Hadjiargyrou M, Simon M, Jurukovski V, Rafailovich MH: Gold nanoparticles cellular toxicity and recovery: effect of size, concentration and exposure time. Nanotoxicology 2010, 4: 120–137. 10.3109/17435390903471463

Wu X, Tan Y, Mao H, Zhang M: Toxic effects of iron oxide nanoparticles on human umbilical vein endothelial cells. Int J Nanomedicine 2010, 5: 385–399.

Mintzer MA, Grinstaff MW: Biomedical applications of dendrimers: a tutorial. Chem Soc Rev 2011, 40: 173–190. 10.1039/b901839p

Nie Y, Zhang ZR, Duan YR: Combined use of polycationic peptide and biodegradable macromolecular polymer as a novel gene delivery system: a preliminary study. Drug Deliv 2006, 13: 441–446. 10.1080/10717540600640302

Pietersz GA, Tang CK, Apostolopoulos V: Structure and design of polycationic carriers for gene delivery. Mini Rev Med Chem 2006, 6: 1285–1298. 10.2174/138955706778992987

Choi KM, Nam HY, Na JH, Kim SW, Kim SY, Kim K, Kwon IC, Ahn HJ: A monitoring method for Atg4 activation in living cells using peptide-conjugated polymeric nanoparticles. Autophagy 2011, 7: 1052–1062. 10.4161/auto.7.9.16451