Advances in Clinical and Experimental Medicine

Title abbreviation: Adv Clin Exp Med
JCR Impact Factor (IF) – 2.1
5-Year Impact Factor – 2.2
Scopus CiteScore – 3.4 (CiteScore Tracker 3.4)
Index Copernicus  – 161.11; MEiN – 140 pts

ISSN 1899–5276 (print)
ISSN 2451-2680 (online)
Periodicity – monthly

Download original text (EN)

Advances in Clinical and Experimental Medicine

2016, vol. 25, nr 1, January-February, p. 151–162

doi: 10.17219/acem/60879

Publication type: review article

Language: English

Download citation:

  • BIBTEX (JabRef, Mendeley)
  • RIS (Papers, Reference Manager, RefWorks, Zotero)

The Nanopharmacology and Nanotoxicology of Nanomaterials: New Opportunities and Challenges

Anna Radomska1,A,B,C,D,E,F, Jarosław Leszczyszyn2,A,B,C,D,E,F, Marek W. Radomski1,3,A,B,C,D,E,F

1 School of Pharmacy and Pharmaceutical Sciences and Trinity Biomedical Sciences Institute, The University of Dublin, Trinity College, Dublin, Ireland

2 Eleonora Reicher National Institute of Geriatrics, Rheumatology and Rehabilitation, Warszawa, Poland

3 Kardio-Med Silesia, Zabrze, Poland

Abstract

The very dynamic growth of nanotechnology, nanomaterials (sized 1–100 nm) and their medical applications over the past 10 years has promised to add a new impetus to the diagnostics and therapeutics of a wide range of human pathologies, including cancer, cardiovascular diseases and diseases of the central nervous system. This growth in nanomedicine also fuels advances in bioengineering, regenerative medicine and the development of medical devices. However, as with all new pharmaceuticals and medical devices, new opportunities are inherently accompanied by new challenges due to the ability of nanomaterials to interact with the body on the cellular, subcellular and molecular levels. This article reviews some of the most compelling problems related to the nanopharmacology and nanotoxicology of nanomaterials. The overview focuses on opportunities emerging from the development of multifunctional nanomaterials and nanotheranostics for the diagnostics and therapy of both major and rare diseases. Challenges related to the hemocompatibility of nanomaterials are also discussed.

Key words

nanotechnology, nanomedicine, pharmacology, toxicology

References (144)

  1. European Commission: Second regulatory review on nanomaterials 2012.
  2. Savolainen K, Backman U, Brouwer D, Fadel B, Fernandes T, Kuhlbusch T, Landsiedel R, Lynch I, Pylkkanen L, Cluster N: Nanosafety in Europe 2015–2025: Towards Safe and Sustainable Nanomaterials and Nanotechnology Innovations. Finnish Institute of Occupational Health 2013.
  3. Medina C, Santos‐Martinez M, Radomski A, Corrigan O, Radomski M: Nanoparticles: pharmacological and toxicological significance. Br J Pharmacol 2007, 150, 552–558.
  4. Barenholz Y: Doxil(R) – the first FDA-approved nano-drug: lessons learned. J Control Release 2012, 160, 117–134.
  5. Dawidczyk CM, Kim C, Park JH, Russell LM, Lee KH, Pomper MG, Searson PC: State-of-the-art in design rules for drug delivery platforms: lessons learned from FDA-approved nanomedicines. J Control Release 2014, 187, 133–144.
  6. Weissig, V, Pettinger, TK, Murdock, N: Nanopharmaceuticals (part 1): products on the market. Int J Nanomedicine 2014, 9, 4357–4373.
  7. Lambert JM: Drug-conjugated antibodies for the treatment of cancer. Br J Clin Pharmacol 2013, 76, 248–262.
  8. Fassas A and Anagnostopoulos A: The use of liposomal daunorubicin (DaunoXome) in acute myeloid leukemia. Leuk Lymphoma 2005, 46, 795–802.
  9. Silverman JA and Deitcher SR: Marqibo(R) (vincristine sulfate liposome injection) improves the pharmacokinetics and pharmacodynamics of vincristine. Cancer Chemother Pharmacol 2013, 71, 555–564.
  10. Kundranda MN and Niu J: Albumin-bound paclitaxel in solid tumors: clinical development and future directions. Drug Des Devel Ther 2015, 9, 3767–3777.
  11. Hafner A, Lovric J, Lakos GP, Pepic I: Nanotherapeutics in the EU: an overview on current state and future directions. Int J Nanomedicine 2014, 9, 1005–1023.
  12. Kim TH, Lee S, Chen X: Nanotheranostics for personalized medicine. Expert Rev Mol Diagn 2013, 13, 257–269.
  13. Gobbo OL, Sjaastad K, Radomski MW, Volkov Y, Prina-Mello A: Magnetic Nanoparticles in Cancer Theranostics. Theranostics 2015, 5, 1249–1263.
  14. Rosen JE, Chan L, Shieh DB, Gu FX: Iron oxide nanoparticles for targeted cancer imaging and diagnostics. Nanomedicine 2012, 8, 275–290.
  15. Yoffe, S, Leshuk, T, Everett, P, Gu, F: Superparamagnetic Iron Oxide Nanoparticles (SPIONs): Synthesis and Surface Modification Techniques for use with MRI and Other Biomedical Applications. Curr Pharm Des 2013, 19, 493–509.
  16. Gobbo OL, Wetterling F, Vaes P, Teughels S, Markos F, Edge D, Shortt CM, Crosbie-Staunton K, Radomski MW, Volkov Y, Prina-Mello A: Biodistribution and pharmacokinetic studies of SPION using particle electron paramagnetic resonance, MRI and ICP-MS. Nanomedicine (Lond) 2015, 10, 1751–1760.
  17. Zapotoczny S, Szczubialka K, Nowakowska M: Nanoparticles in endothelial theranostics: Pharmacological Reports 2015, 67, 751–755.
  18. Mangge H, Almer G, Stelzer I, Reininghaus E, Prassl R: Laboratory medicine for molecular imaging of atherosclerosis. Clin Chim Acta 2014, 437, 19–24.
  19. Palekar RU, Jallouk AP, Lanza GM, Pan H, Wickline SA: Molecular imaging of atherosclerosis with nanoparticlebased fluorinated MRI contrast agents: Nanomedicine (Lond) 2015, 10, 1817–1832.
  20. Lobatto ME, Calcagno C, Millon A, Senders ML, Fay F, Robson PM, Ramachandran S, Binderup T, Paridaans MP, Sensarn S, Rogalla S, Gordon RE, Cardoso L, Storm G, Metselaar JM, Contag CH, Stroes ES, Fayad ZA, Mulder WJ: Atherosclerotic plaque targeting mechanism of long-circulating nanoparticles established by multimodal imaging. ACS Nano 2015, 9, 1837–1847.
  21. Palekar RU, Jallouk AP, Goette MJ, Chen J, Myerson JW, Allen JS, Akk A, Yang L, Tu Y, Miller MJ, Pham CT, Wickline SA, Pan H: Quantifying progression and regression of thrombotic risk in experimental atherosclerosis. Faseb J 2015, 29, 3100–3109.
  22. Kasabach, HHM and Merritt, KK: Capillary hemangioma with extensive purpura. Report of a case. Am J Dis Child 1940, 59, 1063–1070.
  23. National Organization for Rare Disorders, NORD. In: http://rarediseases.org/.
  24. Adams DM and Hammill A: Other vascular tumors: Semin Pediatr Surg 2014, 23, 173–177.
  25. Hall GW: Kasabach-Merritt syndrome: pathogenesis and management: Br J Haematol 2001, 112, 851–862.
  26. Colmenero I and Hoeger PH: Vascular tumours in infants. Part II: vascular tumours of intermediate malignancy [corrected] and malignant tumours: Br J Dermatol 2014, 171, 474–484.
  27. Cockburn A, Bradford R, Buck N, Constable A, Edwards G, Haber B, Hepburn P, Howlett J, Kampers F, Klein C, Radomski M, Stamm H, Wijnhoven S, Wildemann T: Approaches to the safety assessment of engineered nanomaterials (ENM) in food. Food Chem Toxicol 2012, 50, 2224–2242.
  28. Medina C, Santos-Martinez MJ, Radomski A, Corrigan OI, Radomski MW: Nanoparticles: pharmacological and toxicological significance. Br J Pharmacol 2007, 150, 552–558.
  29. Lundqvist M, Stigler J, Elia G, Lynch, I, Cedervall T, Dawson KA: Nanoparticle size and surface properties determine the protein corona with possible implications for biological impacts. Proc Natl Acad Sci USA 2008, 105, 14265–14270.
  30. Lesniak A, Salvati, A, Santos-Martinez MJ, Radomski MW, Dawson KA, Aberg C: Nanoparticle adhesion to the cell membrane and its effect on nanoparticle uptake efficiency. J Am Chem Soc 2013, 135, 1438–1444.
  31. Radomski A, Jurasz P, Alonso-Escolano D, Drews M, Morandi M, Malinski T, Radomski MW: Nanoparticle-induced platelet aggregation and vascular thrombosis. Br J Pharmacol 2005, 146, 882–893.
  32. Gaffney AM, Santos-Martinez MJ, Satti A, Major TC, Wynne KJ, Gun’ko YK, Annich GM, Elia G, Radomski MW: Blood biocompatibility of surface-bound multi-walled carbon nanotubes. Nanomedicine 2015, 11, 39–46.
  33. Corbalan JJ, Medina C, Jacoby A, Malinski T, Radomski MW: Amorphous silica nanoparticles aggregate human platelets: potential implications for vascular homeostasis. Int J Nanomedicine 2012, 7, 631–639.
  34. Santos-Martinez MJ, Rahme K, Corbalan JJ, Faulkner C, Holmes JD, Tajber L, Medina C, Radomski MW: Pegylation increases platelet biocompatibility of gold nanoparticles. J Biomed Nanotechnol 2014, 10, 1004–1015.
  35. Samuel SP, Santos-Martinez MJ, Medina C, Jain N, Radomski MW, Prina-Mello A, Volkov Y: CdTe quantum dots induce activation of human platelets: implications for nanoparticle hemocompatibility. Int J Nanomedicine 2015, 2723–2734.
  36. Li X, Radomski A, Corrigan OI, Tajber L, De Sousa Menezes F, Endter S, Medina C, Radomski MW: Platelet compatibility of PLGA, chitosan and PLGA-chitosan nanoparticles. Nanomedicine (Lond) 2009, 4, 735–746.
  37. Corbalan JJ, Medina C, Jacoby A, Malinski T, Radomski MW: Amorphous silica nanoparticles trigger nitric oxide/peroxynitrite imbalance in human endothelial cells: inflammatory and cytotoxic effects. Int J Nanomedicine 2011, 6, 2821–2835.
  38. Tomaszewski KA, Radomski MW, Santos-Martinez MJ: Nanodiagnostics, nanopharmacology and nanotoxicology of platelet-vessel wall interactions. Nanomedicine (Lond) 2015, 10, 1451–1475.
  39. Bazou, D, Santos-Martinez, MJ, Medina, C, Radomski, MW: Elucidation of flow-mediated tumour cell-induced platelet aggregation using an ultrasound standing wave trap. Br J Pharmacol 2011, 162, 1577–1589.
  40. Santos-Martinez MJ, Inkielewicz-Stepniak I, Medina C, Rahme K, D’Arcy DM, Fox D, Holmes JD, Zhang H, Radomski MW: The use of quartz crystal microbalance with dissipation (QCM-D) for studying nanoparticle-induced platelet aggregation. Int J Nanomedicine 2012, 7, 243–255.
  41. Santos-Martinez MJ, Prina-Mello A, Medina C, Radomski MW: Analysis of platelet function: role of microfluidics and nanodevices. Analyst 2011, 136, 5120–5126.
  42. Santos-Martinez MJ, Tomaszewski KA, Medina C, Bazou D, Gilmer JF, Radomski MW: Pharmacological characterization of nanoparticle-induced platelet microaggregation using quartz crystal microbalance with dissipation: comparison with light aggregometry. Int J Nanomedicine 2015, 10, 5107–5119.
  43. Del Pino P: Tailoring the interplay between electromagnetic fields and nanomaterials toward applications in life sciences: a review. J Biomed Opt 2014, 19, 101507–101517.
  44. Hofmann-Amtenbrink M, Hofmann H, Hool A, Roubert F: Nanotechnology in medicine: European research and its implications. Swiss Medical Weekly 2014, 144, w14044.
  45. Chin-Chan M, Navarro-Yepes J, Quintanilla-Vega B: Environmental pollutants as risk factors for neurodegenerative disorders: Alzheimer and Parkinson diseases. Front Cell Neurosci 2015, 9, 124.
  46. Ikuma K, Decho AW, Lau BL: When nanoparticles meet biofilms-interactions guiding the environmental fate and accumulation of nanoparticles. Front Microbiol 2015, 6, 591.
  47. Sanchez-Quiles D and Tovar-Sanchez A: Are sunscreens a new environmental risk associated with coastal tourism? Environ Int 2015, 83, 158–170.
  48. Niska K, Pyszka K, Tukaj C, Wozniak M, Radomski MW, Inkielewicz-Stepniak I: Titanium dioxide nanoparticles enhance production of superoxide anion and alter the antioxidant system in human osteoblast cells. Int J Nanomedicine 2015, 10, 1095–1107.
  49. Niska K, Santos-Martinez MJ, Radomski MW, Inkielewicz-Stepniak I: CuO nanoparticles induce apoptosis by impairing the antioxidant defense and detoxification systems in the mouse hippocampal HT22 cell line: protective effect of crocetin. Toxicol In Vitr 2015, 29, 663–671.
  50. Grieger KD, Linkov I, Hansen SF, Baun A: Environmental risk analysis for nanomaterials: review and evaluation of frameworks. Nanotoxicology 2012, 6, 196–212.
  51. Holden PA, Nisbet RM, Lenihan HS, Miller RJ, Cherr GN, Schime, JP, Gardea-Torresdey JL: Ecological nanotoxicology: integrating nanomaterial hazard considerations across the subcellular, population, community, and ecosystems levels. Acc Chem Res 2013, 46, 813–822.
  52. Johnston H, Pojana G, Zuin S, Jacobsen NR, Moller P, Loft S, Semmler-Behnke M, McGuiness C, Balharry D, Marcomini A, Wallin H, Kreyling W Donaldson K, Tran L, Stone V: Engineered nanomaterial risk. Lessons learnt from completed nanotoxicology studies: potential solutions to current and future challenges. Crit Rev Toxicol 2013, 43, 1–20.
  53. Ali-Boucetta H and Kostarelos K: Pharmacology of carbon nanotubes: toxicokinetics, excretion and tissue accumulation. Adv Drug Deliv Rev 2013, 65, 2111–2119.
  54. Allen TM and Cullis PR: Liposomal drug delivery systems: from concept to clinical applications. Adv Drug Deliv Rev 2013, 65, 36–48.
  55. Alvarim LT, Nucci LP, Mamani JB, Marti LC, Aguiar MF, Silva HR, Silva GS, Nucci-da-Silva MP, DelBel EA, Gamarra LF: Therapeutics with SPION-labeled stem cells for the main diseases related to brain aging: a systematic review. Int J Nanomedicine 2014, 9, 3749–3770.
  56. Andersen AJ, Wibroe PP, Moghimi SM: Perspectives on carbon nanotube-mediated adverse immune effects. Adv Drug Deliv Rev 2012, 64, 1700–1705.
  57. Arora S, Rajwade JM, Paknikar KM: Nanotoxicology and in vitro studies: the need of the hour. Toxicol Appl Pharmacol 2012. 258, 151–165.
  58. Bao G, Mitragotri S, Tong S: Multifunctional nanoparticles for drug delivery and molecular imaging. Annu Rev Biomed Eng 2013, 15, 253–282.
  59. Bartneck M, Warzecha KT, Tacke F: Therapeutic targeting of liver inflammation and fibrosis by nanomedicine. Hepatobiliary Surg Nutr 2014, 3, 364–376.
  60. Benetti, F Bregoli L, Olivato I, Sabbioni E: Effects of metal(loid)-based nanomaterials on essential element homeostasis: the central role of nanometallomics for nanotoxicology. Metallomics 2014, 6, 729–747.
  61. BeruBe K, Balharry D, Sexton K, Koshy L, Jones T: Combustion-derived nanoparticles: mechanisms of pulmonary toxicity. Clin Exp Pharmacol Physiol 2007, 34, 1044–1050.
  62. Billi F, Campbell P: Nanotoxicology of metal wear particles in total joint arthroplasty: a review of current concepts. J Appl Biomater Biomech 2010, 8, 1–6.
  63. Bussy C, Methven L, Kostarelos K: Hemotoxicity of carbon nanotubes. Adv Drug Deliv Rev 2013, 65, 2127–2134.
  64. Caputo F, De Nicola M, Ghibelli L: Pharmacological potential of bioactive engineered nanomaterials. Biochem Pharmacol 2014, 92, 112–130.
  65. Caracciolo G: Liposome-protein corona in a physiological environment: challenges and opportunities for targeted delivery of nanomedicines. Nanomedicine 2015, 11, 543–557.
  66. Chaudhury K, Kumar V, Kandasamy J, RoyChoudhury S: Regenerative nanomedicine: current perspectives and future directions. Int J Nanomedicine 2014, 9, 4153–4167.
  67. Chen DW and Liu SJ: Nanofibers used for delivery of antimicrobial agents. Nanomedicine (Lond) 2015, 10, 1959–1971.
  68. Chen F, Ehlerding EB, Cai W: Theranostic nanoparticles. J Nucl Med 2014, 55, 1919–1922.
  69. Chen C, Li YF, Qu Y, Chai Z, Zhao Y: Advanced nuclear analytical and related techniques for the growing challenges in nanotoxicology. Chem Soc Rev 2013, 42, 8266–8303.
  70. Cheng CJ, Tietjen GT, Saucier-Sawyer JK, Saltzman WM: A holistic approach to targeting disease with polymeric nanoparticles. Nat Rev Drug Discov 2015, 14, 239–247.
  71. Conde J and Artzi N: The next generation of smart gold nanobeacons: nanotheranostics is ready for prime time. Nanomedicine (Lond) 2015, 10, 1535–1538.
  72. Costa RR, Alatorre-Meda M, Mano JF: Drug nano-reservoirs synthesized using layer-by-layer technologies. Biotechnol Adv 2015.
  73. Das Neves J, Nunes R, Machado A, Sarmento B: Polymer-based nanocarriers for vaginal drug delivery. Adv Drug Deliv Rev 2014.
  74. De Vries R, Andrade CAS, Bakuzis AF, Mandal SM, Franco OL: Next-generation nanoantibacterial tools developed from peptides. Nanomedicine 2015, 10, 1643–1661.
  75. Deshayes S and Gref R: Synthetic and bioinspired cage nanoparticles for drug delivery. Nanomedicine (Lond) 2014, 9, 1545–1564.
  76. Doktorovova S, Souto EB, Silva AM: Nanotoxicology applied to solid lipid nanoparticles and nanostructured lipid carriers – a systematic review of in vitro data. Eur J Pharm Biopharm 2014, 87, 1–18.
  77. Donaldson K, Poland CA, Schins RP: Possible genotoxic mechanisms of nanoparticles: criteria for improved test strategies. Nanotoxicology 2010, 4, 414–420.
  78. Donaldson K, Duffin R, Langrish JP, Miller MR, Mills NL, Poland CA, Raftis J, Shah A, Shaw CA, Newby DE: Nanoparticles and the cardiovascular system: a critical review. Nanomedicine (Lond) 2013, 8, 403–423.
  79. Estelrich J, Sanchez-Martin MJ, Busquets MA: Nanoparticles in magnetic resonance imaging: from simple to dual contrast agents. Int J Nanomedicine 2015, 10, 1727–1741.
  80. Feng, XL Chen AJ, Zhang YL, Wang JF, Shao LQ, Wei LM: Application of dental nanomaterials: potential toxicity to the central nervous system. Int J Nanomedicine 2015, 10, 3547–3565.
  81. Fernandes E, Ferreira JA, Andreia P, Luis L, Barroso, S, Sarmento B, Santos LL: New trends in guided nanotherapies for digestive cancers: A systematic review. J Control Release 2015, 209, 288–307.
  82. Franci G, Falanga A, Galdiero S, Palomba L, Rai, M, Morelli G, Galdiero M: Silver nanoparticles as potential antibacterial agents. Molecules 2015, 20, 8856–8874.
  83. Frohlich E: Value of phagocyte function screening for immunotoxicity of nanoparticles in vivo. Int J Nanomedicine 2015, 10, 3761–3778.
  84. Fubini B, Ghiazza M, Fenoglio I: Physico-chemical features of engineered nanoparticles relevant to their toxicity. Nanotoxicology 2010, 4, 347–363.
  85. Gainza G, Villullas S, Pedraz JL, Hernandez RM, Igartua M: Advances in drug delivery systems (DDSs) to release growth factors for wound healing and skin regeneration. Nanomedicine 2015, 11, 1551–1573.
  86. Gendelman HE, Anantharam V, Bronich T, Ghaisas S, Jin H, Kanthasamy AG, Liu X, McMillan J, Mosley RL, Narasimhan B, Mallapragada SK: Nanoneuromedicines for degenerative, inflammatory, and infectious nervous system diseases. Nanomedicine 2015, 11, 751–767.
  87. Gharagozloo M, Majewski S, Foldvari M: Therapeutic applications of nanomedicine in autoimmune diseases: from immunosuppression to tolerance induction. Nanomedicine 2015, 11, 1003–1018.
  88. Gregori M, Masserini M, Mancini S: Nanomedicine for the treatment of Alzheimer’s disease. Nanomedicine (Lond) 2015, 10, 1203–1218.
  89. Guo S, Huang L: Nanoparticles containing insoluble drug for cancer therapy. Biotechnol Adv 2014, 32, 778–788.
  90. Gusic N, Ivkovic A, VaFaye J, Vukasovic A, Ivkovic J, Hudetz D, Jankovic S: Nanobiotechnology and bone regeneration: a mini-review. Int Orthop 2014, 38, 1877–1884.
  91. Holden PA, Schimel JP, Godwin HA: Five reasons to use bacteria when assessing manufactured nanomaterial environmental hazards and fates. Current Opinion in Biotechnology 2014, 27, 73–78.
  92. Hristozov DR, Zabeo A, Foran C, Isigonis P, Critto, A, Marcomini A, Linkov I: A weight of evidence approach for hazard screening of engineered nanomaterials. Nanotoxicology 2014, 8, 72–87.
  93. Hubbs AF, Sargent LM, Porte, DW, Sager TM, Chen BT, Frazer DG, Castranova V, Sriram K, Nurkiewicz TR, Reynolds SH, Battelli LA, Schwegler-Berry D, McKinney W, Fluharty KL, Mercer RR: Nanotechnology: toxicologic pathology. Toxicol Pathol 2013, 41, 395–409.
  94. Ilinskaya AN and Dobrovolskaia MA: Nanoparticles and the blood coagulation system. Part II: safety concerns. Nanomedicine (Lond) 2013, 8, 969–981.
  95. Ilinskaya AN and Dobrovolskaia MA: Nanoparticles and the blood coagulation system. Part I: benefits of nanotechnology. Nanomedicine (Lond) 2013, 8, 773–784.
  96. Jo DH, Kim JH, Lee TG, Kim JH: Size, surface charge, and shape determine therapeutic effects of nanoparticles on brain and retinal diseases. Nanomedicine 2015.
  97. Kandi V and Kandi S: Antimicrobial properties of nanomolecules: potential candidates as antibiotics in the era of multi-drug resistance. Epidemiol Health 2015, 37, e2015020.
  98. Kermanizadeh A, Chauche C, Brown DM, Loft S, Moller P: The role of intracellular redox imbalance in nanomaterial induced cellular damage and genotoxicity: a review. Environ Mol Mutagen 2015, 56, 111–124.
  99. Kim YD, Park TE, Singh B, Maharjan S, Choi YJ, Choung PH, Arote RB, Cho CS: Nanoparticle-mediated delivery of siRNA for effective lung cancer therapy. Nanomedicine (Lond) 2015, 10, 1165–1188.
  100. Kodiha M, Wang YM, Hutter E, Maysinger D, Stochaj U: Off to the organelles – killing cancer cells with targeted gold nanoparticles. Theranostics 2015, 5, 357–370.
  101. Lakkakula JR and Macedo Krause RW: A vision for cyclodextrin nanoparticles in drug delivery systems and pharmaceutical applications. Nanomedicine (Lond) 2014, 9, 877–894.
  102. Landriscina A, Rosen J, Friedman AJ: Biodegradable chitosan nanoparticles in drug delivery for infectious disease. Nanomedicine (Lond) 2015, 10, 1609–1619.
  103. Larson JK, Carvan MJ 3rd, Hutz RJ: Engineered nanomaterials: an emerging class of novel endocrine disruptors. Biol Reprod 2014, 91, 1–8.
  104. Laurent S, Saei AA, Behzadi S, Panahifar A, Mahmoudi M: Superparamagnetic iron oxide nanoparticles for delivery of therapeutic agents: opportunities and challenges. Expert Opin Drug Deliv 2014, 11, 1449–1470.
  105. Li Y, Dong H, Li Y, Shi D: Graphene-based nanovehicles for photodynamic medical therapy. Int J Nanomedicine 2015, 10, 2451–2459.
  106. Li YF, Zhao J, Qu Y, Gao Y, Guo Z, Liu Z, Zhao Y, Chen C: Synchrotron radiation techniques for nanotoxicology. Nanomedicine 2015, 11, 1531–1549.
  107. Lukowiak MC, Thota BN, Haag R: Dendritic core-shell systems as soft drug delivery nanocarriers. Biotechnol Adv 2015.
  108. Lux F, Sancey L, Bianchi A, Cremillieux Y, Roux S, Tillement O: Gadolinium-based nanoparticles for theranostic MRI-radiosensitization. Nanomedicine (Lond) 2015, 10, 1801–1815.
  109. Madl AK, Liong M, Kovochich M, Finley BL, Paustenbach DJ, Oberdorster G: Toxicology of wear particles of cobalt-chromium alloy metal-on-metal hip implants Part I: Physicochemical properties in patient and simulator studies. Nanomedicine 2015, 11, 1201–1215.
  110. Madl AK, Kovochich M, Liong M, Finley BL, Paustenbach DJ, Oberdorster G: Toxicology of wear particles of cobalt-chromium alloy metal-on-metal hip implants Part II: Importance of physicochemical properties and dose in animal and in vitro studies as a basis for risk assessment. Nanomedicine 2015, 11, 1285–1298.
  111. Mottaghitalab F, Farokhi M, Shokrgozar MA, Atyabi F, Hosseinkhani H: Silk fibroin nanoparticle as a novel drug delivery system. J Control Release 2015, 206, 161–176.
  112. Mulder WJ, Jaffer FA, Fayad ZA, Nahrendorf M: Imaging and nanomedicine in inflammatory atherosclerosis. Sci Transl Med 2014, 6, 239.
  113. ] Muller RH, Gohla S, Keck CM: State of the art of nanocrystals – special features, production, nanotoxicology aspects and intracellular delivery. Eur J Pharm Biopharm 2011, 78, 1–9.
  114. Murugan K, Choonara YE, Kumar P, Bijukumar D, du Toit LC, Pillay V: Parameters and characteristics governing cellular internalization and trans-barrier trafficking of nanostructures. Int J Nanomedicine 2015, 10, 2191–2206.
  115. Nel AE: Implementation of alternative test strategies for the safety assessment of engineered nanomaterials. J Intern Med, 2013, 274, 561–577.
  116. Nel A Xia T, Meng H, Wang X, Lin S, Ji Z, Zhang H: Nanomaterial toxicity testing in the 21st century: use of a predictive toxicological approach and high-throughput screening. Acc Chem Res 2013, 46, 607–621.
  117. Nielsen OH: New strategies for treatment of inflammatory bowel disease. Front Med (Lausanne) 2014, 1, 3.
  118. Nunez-Anita RE, Acosta-Torres LS, Vilar-Pineda J, Martinez-Espinosa JC, de la Fuente-Hernandez J, Castano VM: Toxicology of antimicrobial nanoparticles for prosthetic devices. Int J Nanomedicine 2014, 9, 3999–4006.
  119. Osmond MJ and McCall MJ: Zinc oxide nanoparticles in modern sunscreens: an analysis of potential exposure and hazard. Nanotoxicology 2010, 4, 15–41.
  120. Panzarini E and Dini L: Nanomaterial-induced autophagy: a new reversal MDR tool in cancer therapy? Mol Pharm 2014, 11, 2527–2538.
  121. Paul A: Nanocomposite hydrogels: an emerging biomimetic platform for myocardial therapy and tissue engineering. Nanomedicine (Lond) 2015, 10, 1371–1374.
  122. Polak P and Shefi O: Nanometric agents in the service of neuroscience: Manipulation of neuronal growth and activity using nanoparticles. Nanomedicine 2015, 11, 1467–1479.
  123. Sadikot RT: The potential role of nanoand micro-technology in the management of critical illnesses. Adv Drug Deliv Rev 2014, 77, 27–31.
  124. Schrofel A, Kratosova G, Safarik I, Safarikova M, Raska I, Shor LM: Applications of biosynthesized metallic nanoparticles – a review. Acta Biomater 2014, 10, 4023–4042.
  125. Sehedic D, Cikankowitz A, Hindre F, Davodeau F, Garcion E: Nanomedicine to overcome radioresistance in glioblastoma stem-like cells and surviving clones. Trends Pharmacol Sci 2015, 36, 236–252.
  126. Shvedova AA, Kagan VE: The role of nanotoxicology in realizing the ‘helping without harm’ paradigm of nanomedicine: lessons from studies of pulmonary effects of single-walled carbon nanotubes. J Intern Med 2010, 267, 106–118.
  127. Sosnik A, Carcaboso AM: Nanomedicines in the future of pediatric therapy. Adv Drug Deliv Rev 2014, 73, 140–161.
  128. Sriraman SK, Aryasomayajula B, Torchilin VP: Barriers to drug delivery in solid tumors. Tissue Barriers 2014, 2, e29528.
  129. Tan A, Yildirimer L, Rajadas J, De La Pena H, Pastorin G, Seifalian A: Quantum dots and carbon nanotubes in oncology: a review on emerging theranostic applications in nanomedicine. Nanomedicine (Lond) 2011, 6, 1101–1114.
  130. Torchilin VP: Multifunctional, stimuli-sensitive nanoparticulate systems for drug delivery. Nat Rev Drug Discov 2014, 13, 813–827.
  131. Tseng YY and Liu SJ: Nanofibers used for the delivery of analgesics. Nanomedicine (Lond) 2015, 10, 1785–1800.
  132. Veiseh O, Tang BC, Whitehead KA, Anderson DG, Langer R: Managing diabetes with nanomedicine: challenges and opportunities Nat Rev Drug Discov 2015, 14, 45–57.
  133. Vellayappan MV, Balaji A, Subramanian AP, John AA, Jaganathan SK, Murugesan S, Supriyanto E, Yusof M: Multifaceted prospects of nanocomposites for cardiovascular grafts and stents. Int J Nanomedicine 2015, 10, 2785–2803.
  134. Vinogradov S, Warren G, Wei X: Macrophages associated with tumors as potential targets and therapeutic intermediates. Nanomedicine (Lond) 2014, 9, 695–707.
  135. Walmsley GG, McArdle A, Tevlin R, Momeni A, Atashroo D, Hu MS, Feroze AH, Wong VW, Lorenz PH, Longaker MT, Wan DC: Nanotechnology in bone tissue engineering. Nanomedicine 2015, 11, 1253–1263.
  136. Wang J, Wu W, Jiang X: Nanoscaled boron-containing delivery systems and therapeutic agents for cancer treatment. Nanomedicine (Lond) 2015, 10, 1149–1163.
  137. Weissig V, Guzman-Villanueva D: Nanopharmaceuticals (part 2): products in the pipeline. Int J Nanomedicine 2015, 10, 1245–1257.
  138. White-Schenk D, Shi R, Leary JF: Nanomedicine strategies for treatment of secondary spinal cord injury. Int J Nanomedicine 2015, 10, 923–938.
  139. Winkler DA, Mombelli E, Pietroiusti A, Tran L, Worth A, Fadeel B, McCal, MJ: Applying quantitative structureactivity relationship approaches to nanotoxicology: current status and future potential. Toxicology 2013, 313, 15–23.
  140. Zhao H, Li Y, Hu Y: Nanotechnologies in glycoproteomics. Clin Proteomics 2014, 11, 21.
  141. Zhen Z, Tang W, Todd T, Xie J: Ferritins as nanoplatforms for imaging and drug delivery. Expert Opin Drug Deliv 2014, 11, 1913–1922.
  142. Wang J, O’Sullivan, S, Harmon S, Keaveny R, Radomski MW, Medina C, Gilmer JF: Design of barbituratenitrate hybrids that inhibit MMP-9 activity and secretion. J Med Chem 2012, 55, 2154–2162.
  143. Chung A, Wildhirt SM, Wang S, Koshal A, Radomsk, MW: Combined administration of nitric oxide gas and iloprost during cardiopulmonary bypass reduces platelet dysfunction: a pilot clinical study. J Thorac Cardiovasc Surg 2005, 129, 782–790.
  144. ] Saito M, Gunji Y, Kashii Y, Odaka J, Yamauchi T, Kanai N, Momoi MY: Refractory kaposiform hemangioendothelioma that expressed vascular endothelial growth factor receptor (VEGFR)-2 and VEGFR-3: a case report. J Pediatr Hematol Oncol 2009, 31, 194–197.
© Wroclaw Medical University