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Nanoparticle-Based Medicines: A Review of FDA-Approved Materials and Clinical Trials to Date

ABSTRACT

In this review we provide an up to date snapshot of nanomedicines either currently approved by the US FDA, or in the FDA clinical trials process. We define nanomedicines as therapeutic or imaging agents which comprise a nanoparticle in order to control the biodistribution, enhance the efficacy, or otherwise reduce toxicity of a drug or biologic. We identified 51 FDA-approved nanomedicines that met this definition and 77 products in clinical trials, with ~40% of trials listed in clinicaltrials.gov started in 2014 or 2015. While FDA approved materials are heavily weighted to polymeric, liposomal, and nanocrystal formulations, there is a trend towards the development of more complex materials comprising micelles, protein-based NPs, and also the emergence of a variety of inorganic and metallic particles in clinical trials. We then provide an overview of the different material categories represented in our search, highlighting nanomedicines that have either been recently approved, or are already in clinical trials. We conclude with some comments on future perspectives for nanomedicines, which we expect to include more actively-targeted materials, multi-functional materials (“theranostics”) and more complicated materials that blur the boundaries of traditional material categories. A key challenge for researchers, industry, and regulators is how to classify new materials and what additional testing (e.g. safety and toxicity) is required before products become available.

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Fig. 1

Abbreviations

CHOP:

Chemotherapy containing cyclophosmphamide, doxorubicin, vincristine, and prednisolone

CKD:

Chronic Kidney Disease

CMC:

Critical micelle concentration

cRGDY:

Cyclic arginine-glycine-aspartic acid

EPR:

Enhanced permeability and retention

IDE:

Investigational device exemption

IND:

Investigational New Drug

MTAs:

Molecularly targeted agents

NABs:

Albumin bound nanoparticles

NCL:

Nanotechnology Characterization Laboratory

NDA:

New Drug Application

NIR:

Near-infrared

NP:

Nanoparticle

PEG:

Poly (ethylene glycol)

PLGA:

Polyactide-co-glycolic acid

PPX:

Poliglumex

PSMA:

Prostate-specific membrane antigen

PTCL:

Peripheral T-cell lymphomas

REFERENCES

  1. Albanese A, Tang PS, Chan WCW. The effect of nanoparticle size, shape, and surface chemistry on biological systems. Annu Rev Biomed Eng. 2012;14:1–16.

    CAS  Article  PubMed  Google Scholar 

  2. Chaudhuri RG, Paria S. Core/Shell nanoparticles: classes, properties, synthesis mechanisms, characterization, and applications. Chem Rev. 2012;112(4):2373–433.

    Article  Google Scholar 

  3. Cimalla P, Werner T, Gaertner M, Mueller C, Walther J, Wittig D, et al. Magnetomotive imaging of iron oxide nanoparticles as cellular contrast agents for optical coherence tomography. Proc Spie. 2013;8802.

  4. Dreaden EC, Alkilany AM, Huang X, Murphy CJ, El-Sayed MA. The golden age: gold nanoparticles for biomedicine. Chem Soc Rev. 2012;41(7):2740–79.

    CAS  Article  PubMed  Google Scholar 

  5. Elsabahy M, Wooley KL. Design of polymeric nanoparticles for biomedical delivery applications. Chem Soc Rev. 2012;41(7):2545–61.

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  6. Kamaly N, Xiao Z, Valencia PM, Radovic-Moreno AF, Farokhzad OC. Targeted polymeric therapeutic nanoparticles: design, development and clinical translation. Chem Soc Rev. 2012;41(7):2971–3010.

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  7. Tang F, Li L, Chen D. Mesoporous silica nanoparticles: synthesis, biocompatibility and drug delivery. Adv Mater. 2012;24(12):1504–34.

    CAS  Article  PubMed  Google Scholar 

  8. Eifler AC, Thaxton CS. Nanoparticle therapeutics: FDA approval, clinical trials, regulatory pathways, and case study. In: Hurst SJ, editor. Biomedical nanoetechnology: methods and protocols. methods in molecular biology. 7262011. p. 325–38.

  9. Etheridge ML, Campbell SA, Erdman AG, Haynes CL, Wolf SM, McCullough J. The big picture on nanomedicine: the state of investigational and approved nanomedicine products. Nanomed-Nanotechnol Biology and Med. 2013;9(1):1–14.

    CAS  Article  Google Scholar 

  10. Nel AE, Maedler L, Velegol D, Xia T, Hoek EMV, Somasundaran P, et al. Understanding biophysicochemical interactions at the nano-bio interface. Nat Mater. 2009;8(7):543–57.

    CAS  Article  PubMed  Google Scholar 

  11. Rolfe BE, Blakey I, Squires O, Peng H, Boase NRB, Alexander C, et al. Multimodal polymer nanoparticles with combined F-19 magnetic resonance and optical detection for tunable, targeted, multimodal imaging in vivo. J Am Chem Soc. 2014;136(6):2413–9.

    CAS  Article  PubMed  Google Scholar 

  12. Choi HS, Liu W, Misra P, Tanaka E, Zimmer JP, Ipe BI, et al. Renal clearance of quantum dots. Nat Biotechnol. 2007;25(10):1165–70.

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  13. Fox ME, Szoka FC, Frechet JMJ. Soluble polymer carriers for the treatment of cancer: the importance of molecular architecture. Acc Chem Res. 2009;42(8):1141–51.

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  14. Sadauskas E, Wallin H, Stoltenberg M, Vogel U, Doering P, Larsen A, et al. Kupffer cells are central in the removal of nanoparticles from the organism. Part Fibre Toxicol. 2007;4:10.

    Article  PubMed  PubMed Central  Google Scholar 

  15. Tenzer S, Docter D, Rosfa S, Wlodarski A, Kuharev J, Rekik A, et al. Nanoparticle size is a critical physicochemical determinant of the human blood plasma corona: a comprehensive quantitative proteomic analysis. ACS Nano. 2011;5(9):7155–67.

    CAS  Article  PubMed  Google Scholar 

  16. Duncan R, Sat YN. Tumour targeting by enhanced permeability and retention (EPR) effect. Ann Oncol. 1998;9:39.

    Article  Google Scholar 

  17. Casi G, Neri D. Antibody–drug conjugates: basic concepts, examples and future perspectives. J Control Release. 2012;161(2):422–8.

    CAS  Article  PubMed  Google Scholar 

  18. Diamantis N, Banerji U. Antibody-drug conjugates—an emerging class of cancer treatment. Br J Cancer. 2016;114(4):362–7.

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  19. Tinkle S, McNeil SE, Muehlebach S, Bawa R, Borchard G, Barenholz Y, et al. Nanomedicines: addressing the scientific and regulatory gap. Ann Reports. 2014;1313:35–56.

    CAS  Google Scholar 

  20. Dobrovolskaia MA. Pre-clinical immunotoxicity studies of nanotechnology-formulated drugs: challenges, considerations and strategy. J Control Release. 2015;220:571–83.

    CAS  Article  PubMed  Google Scholar 

  21. Nanotechnology Characterization Laboratory: National Cancer Institute US National Institues of Health; 2016 [2/16/2016]. Available from: http://ncl.cancer.gov/.

  22. NCT02549248: Nanoparticles Analysis in Lung and Bronchi During Various Pulmonary Interstitial Diseases and Relationships With Their Aetiology (NANOPI) [Full text view]. Available from: ClinicalTrials.gov.

  23. Registered Clinical Trial Database [Internet]. 2016 [cited 2/15/2016]. Available from: https://clinicaltrials.gov/.

  24. Schutz CA, Juillerat-Jeanneret L, Mueller H, Lynch I, Riediker M, Consortium N. Therapeutic nanoparticles in clinics and under clinical evaluation. Nanomedicine-Uk. 2013;8(3):449–67.

    Article  Google Scholar 

  25. Svenson S. What nanomedicine in the clinic right now really forms nanoparticles? Wiley Interdisciplinary Reviews. Nanomed Nanobiotechnol. 2014;6(2):125–35.

    CAS  Article  Google Scholar 

  26. Zhang L, Gu FX, Chan JM, Wang AZ, Langer RS, Farokhzad OC. Nanoparticles in medicine: therapeutic applications and developments. Clin Pharmacol Ther. 2008;83(5):761–9.

    CAS  Article  PubMed  Google Scholar 

  27. Cures P. Neglected disease research and development: is the global financial crisis changing R&D. London: Policy Cures; 2011.

    Google Scholar 

  28. Tsoulfas G. The impact of the European financial crisis on clinical research within the European union or “when life gives you lemons, make lemonade”. Hippokratia. 2012;16(1):6–10.

    CAS  PubMed  PubMed Central  Google Scholar 

  29. Cui JW, van Koeverden MP, Mullner M, Kempe K, Caruso F. Emerging methods for the fabrication of polymer capsules. Adv Colloid Interf Sci. 2014;207:14–31.

    CAS  Article  Google Scholar 

  30. Duncan R. Polymer therapeutics: Top 10 selling pharmaceuticals - What next? J Control Release. 2014;190:371–80.

    CAS  Article  PubMed  Google Scholar 

  31. Johnson KP, Brooks BR, Cohen JA, Ford CC, Goldstein J, Lisak RP, et al. Extended use of glatiramer acetate (Copaxone) is well tolerated and maintains its clinical effect on multiple sclerosis relapse rate and degree of disability. Neurology. 1998;50(3):701–8.

    CAS  Article  PubMed  Google Scholar 

  32. Alconcel SNS, Baas AS, Maynard HD. FDA-approved poly(ethylene glycol)-protein conjugate drugs. Polym Chem. 2011;2(7):1442–8.

    CAS  Article  Google Scholar 

  33. Benbrook DM. Biotechnology and biopharmaceuticals: transforming proteins and genes into drugs, 2nd edition. Clinic infect Dis: Off Publ Infect DisSoc Am. 2015;60(2):331–2.

    Article  Google Scholar 

  34. Hu X, Miller L, Richman S, Hitchman S, Glick G, Liu SF, et al. A novel PEGylated interferon Beta-1a for multiple sclerosis: safety, pharmacology, and biology. J Clin Pharmacol. 2012;52(6):798–808.

    CAS  Article  PubMed  Google Scholar 

  35. Ing M, Gupta N, Teyssandier M, Maillere B, Pallardy M, Delignat S, et al. Immunogenicity of long-lasting recombinant factor VIII products. Cell Immunol. 2016;301:40–8.

    CAS  Article  PubMed  Google Scholar 

  36. Awada A, Garcia AA, Chan S, Jerusalem GHM, Coleman RE, Huizing MT, et al. Two schedules of etirinotecan pegol (NKTR-102) in patients with previously treated metastatic breast cancer: a randomised phase 2 study. Lancet Oncol. 2013;14(12):1216–25.

    CAS  Article  PubMed  Google Scholar 

  37. Paz-Ares L, Ross H, O’Brien M, Riviere A, Gatzemeier U, Von Pawel J, et al. Phase III trial comparing paclitaxel poliglumex vs docetaxel in the second-line treatment of non-small-cell lung cancer. Br J Cancer. 2008;98(10):1608–13.

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  38. Berges R. Eligard (R): Pharmacokinetics, effect on testosterone and PSA levels and tolerability. Eur Urol Suppl. 2005;4(5):20–5.

    CAS  Article  Google Scholar 

  39. Svenson S, Wolfgang M, Hwang J, Ryan J, Eliasof S. Preclinical to clinical development of the novel camptothecin nanopharmaceutical CRLX101. J Control Release. 2011;153(1):49–55.

    CAS  Article  PubMed  Google Scholar 

  40. Oerlemans C, Bult W, Bos M, Storm G, Nijsen JFW, Hennink WE. Polymeric micelles in anticancer therapy: targeting, imaging and triggered release. Pharm Res-Dordr. 2010;27(12):2569–89.

    CAS  Article  Google Scholar 

  41. Taylor DD, Gercel-Taylor C. MicroRNA signatures of tumor-derived exosomes as diagnostic biomarkers of ovarian cancer. Gynecol Oncol. 2008;110(1):13–21.

    CAS  Article  PubMed  Google Scholar 

  42. Hrkach J, Von Hoff D, Ali MM, Andrianova E, Auer J, Campbell T, et al. Preclinical development and clinical translation of a PSMA-targeted docetaxel nanoparticle with a differentiated pharmacological profile. Sci Transl Med. 2012;4(128).

  43. Ashton S, Song YH, Nolan J, Cadogan E, Murray J, Odedra R, et al. Aurora kinase inhibitor nanoparticles target tumors with favorable therapeutic index in vivo. Sci Transl Med. 2016;8(325):325ra17–ra17.

    Article  PubMed  Google Scholar 

  44. Rijcken CJF, Veldhuis TFJ, Ramzi A, Meeldijk JD, van Nostrum CF, Hennink WE. Novel fast degradable thermosensitive polymeric micelles based on PEG-block-poly(N-(2-hydroxyethyl)methacrylamide-oligolactates). Biomacromolecules. 2005;6(4):2343–51.

    CAS  Article  PubMed  Google Scholar 

  45. Davis ME. The first targeted delivery of siRNA in humans via a self-assembling, cyclodextrin polymer-based nanoparticle: from concept to clinic. Mol Pharmaceut. 2009;6(3):659–68.

    CAS  Article  Google Scholar 

  46. Bangham AD, Standish MM, Watkins JC. Diffusion of univalent ions across lamellae of swollen phospholipids. J Mol Biol. 1965;13(1):238.

    CAS  Article  PubMed  Google Scholar 

  47. Allen TM, Cullis PR. Liposomal drug delivery systems: from concept to clinical applications. Adv Drug Deliv Rev. 2013;65(1):36–48.

    CAS  Article  PubMed  Google Scholar 

  48. Vaage J, Mayhew E, Lasic D, Martin F. Therapy of primary and metastatic mouse mammary carcinomas with doxorubicin encapsulated in long circulating. Int J Cancer. 1992;51(6):942–8.

    CAS  Article  PubMed  Google Scholar 

  49. Saif Ur Rehman S, Lim K, Wang-Gillam A. Nanoliposomal irinotecan plus fluorouracil and folinic acid: a new treatment option in metastatic pancreatic cancer. Exp Rev Anticancer Ther. 2016:null-null.

  50. Wang-Gillam A, Li C-P, Bodoky G, Dean A, Shan Y-S, Jameson G, et al. Nanoliposomal irinotecan with fluorouracil and folinic acid in metastatic pancreatic cancer after previous gemcitabine-based therapy (NAPOLI-1): a global, randomised, open-label, phase 3 trial. The Lancet 387(10018):545–57.

  51. James ND, Coker RJ, Tomlinson D, Harris JR, Gompels M, Pinching AJ, et al. Liposomal doxorubicin (Doxil): an effective new treatment for Kaposi’s sarcoma in AIDS. Clin Oncol (Royal College of Radiologists (Great Britain)). 1994;6(5):294–6.

    CAS  Article  Google Scholar 

  52. Gabizon A, Catane R, Uziely B, Kaufman B, Safra T, Cohen R, et al. Prolonged circulation time and enhanced accumulation in malignant exudates of doxorubicin encapsulated in polyethylene-glycol coated liposomes. Cancer Res. 1994;54(4):987–92.

    CAS  PubMed  Google Scholar 

  53. Hann IM, Prentice HG. Lipid-based amphotericin B: a review of the last 10 years of use. Int J Antimicrob Agents. 2001;17(3):161–9.

    CAS  Article  PubMed  Google Scholar 

  54. Arnold J, Kilmartin D, Olson J, Neville S, Robinson K, Laird A, et al. Verteporfin therapy of subfoveal choroidal neovascularization in age-related macular degeneration: Two-year results of a randomized clinical trial including lesions with occult with no classic choroidal neovascularization-verteporfin in photodynamic therapy report 2. Am J Ophthalmol. 2001;131(5):541–60.

    Article  Google Scholar 

  55. May JP, Li S-D. Hyperthermia-induced drug targeting. Exp Opin Drug Deliv. 2013;10(4):511–27.

    CAS  Article  Google Scholar 

  56. Qin L, Wang C-Z, Fan H-J, Zhang C-J, Zhang H-W, Lv M-H, et al. A dual-targeting liposome conjugated with transferrin and arginine-glycine-aspartic acid peptide for glioma-targeting therapy. Oncol Lett. 2014;8(5):2000–6.

    PubMed  PubMed Central  Google Scholar 

  57. Green MR, Manikhas GM, Orlov S, Afanasyev B, Makhson AM, Bhar P, et al. Abraxane((R)), a novel Cremophor((R))-free, albumin-bound particle form of paclitaxel for the treatment of advanced non-small-cell lung cancer. Ann Oncol. 2006;17(8):1263–8.

    CAS  Article  PubMed  Google Scholar 

  58. Desai N, Trieu V, Yao ZW, Louie L, Ci S, Yang A, et al. Increased antitumor activity, intratumor paclitaxel concentrations, and endothelial cell transport of Cremophor-free, albumin-bound paclitaxel, ABI-007, compared with Cremophor-based paclitaxel. Clin Cancer Res. 2006;12(4):1317–24.

    CAS  Article  PubMed  Google Scholar 

  59. Fuentes AC, Szwed E, Spears CD, Thaper S, Dang LH, Dang NH. Denileukin diftitox (Ontak) as maintenance therapy for peripheral T-Cell lymphomas: three cases with sustained remission. Case Pep Oncol Med. 2015;2015:123756.

    Google Scholar 

  60. Foss FM, Sjak-Shie N, Goy A, Jacobsen E, Advani R, Smith MR, et al. A multicenter phase II trial to determine the safety and efficacy of combination therapy with denileukin diftitox and cyclophosphamide, doxorubicin, vincristine and prednisone in untreated peripheral T-cell lymphoma: the CONCEPT study. Leukemia lymphoma. 2013;54(7):1373–9.

    CAS  Article  PubMed  Google Scholar 

  61. Foss F. Clinical experience with Denileukin Diftitox (ONTAK). Semin Oncol. 2006;33(Supplement 3):11–6.

    Article  Google Scholar 

  62. Chawla SP, Chua VS, Fernandez L, Quon D, Blackwelder WC, Gordon EM, et al. Advanced phase I/II studies of targeted gene delivery in vivo: intravenous Rexin-G for gemcitabine-resistant metastatic pancreatic cancer. Mol Ther. 2010;18(2):435–41.

    CAS  Article  PubMed  Google Scholar 

  63. Gordon EM, Hall FL. Rexin-G, a targeted genetic medicine for cancer. Expert Opin Biol Ther. 2010;10(5):819–32.

    CAS  Article  PubMed  Google Scholar 

  64. Salah EDTA, Bakr MM, Kamel HM, Abdel KM. Magnetite nanoparticles as a single dose treatment for iron deficiency anemia. Google Patents. 2010.

  65. Bashir MR, Bhatti L, Marin D, Nelson RC. Emerging applications for ferumoxytol as a contrast agent in MRI. J Magn Reson Imaging. 2015;41(4):884–98.

    Article  PubMed  Google Scholar 

  66. Wang Y-XJ. Current status of superparamagnetic iron oxide contrast agents for liver magnetic resonance imaging. World J Gastroenterol. 2015;21(47):13400–2.

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  67. Thiesen B, Jordan A. Clinical applications of magnetic nanoparticles for hyperthermia. Int J Hyperther. 2008;24(6):467–74.

    CAS  Article  Google Scholar 

  68. Maier-Hauff K, Ulrich F, Nestler D, Niehoff H, Wust P, Thiesen B, et al. Efficacy and safety of intratumoral thermotherapy using magnetic iron-oxide nanoparticles combined with external beam radiotherapy on patients with recurrent glioblastoma multiforme. J Neuro-Oncol. 2011;103(2):317–24.

    Article  Google Scholar 

  69. Kharlamov AN, Gabinsky JL. Plasmonic photothermic and stem cell therapy of atherosclerotic plaque as a novel nanotool for angioplasty and artery remodeling. Rejuvenation Res. 2012;15(2):222–30.

    CAS  Article  PubMed  Google Scholar 

  70. Zeng S, Yu X, Law W-C, Zhang Y, Hu R, Dinh X-Q, et al. Size dependence of Au NP-enhanced surface plasmon resonance based on differential phase measurement. Sensors Actuators B Chem. 2013;176:1128–33.

    CAS  Article  Google Scholar 

  71. Sanders M. A review of controlled clinical trials examining the effects of antimalarial compounds and gold compounds on radiographic progression in rheumatoid arthritis. J Rheumatol. 2000;27(2):523–9.

    CAS  PubMed  Google Scholar 

  72. Tomic S, Dokic J, Vasilijic S, Ogrinc N, Rudolf R, Pelicon P, et al. Size-dependent effects of gold nanoparticles uptake on maturation and antitumor functions of human dendritic cells in vitro. PLoS ONE. 2014;9(5), e96584.

    Article  PubMed  PubMed Central  Google Scholar 

  73. Qiu TA, Bozich JS, Lohse SE, Vartanian AM, Jacob LM, Meyer BM, et al. Gene expression as an indicator of the molecular response and toxicity in the bacterium Shewanella oneidensis and the water flea Daphnia magna exposed to functionalized gold nanoparticles. Environ Sci: Nano. 2015;2(6):615–29.

    CAS  Google Scholar 

  74. Libutti SK, Paciotti GF, Byrnes AA, Alexander Jr HR, Gannon WE, Walker M, et al. Phase I and pharmacokinetic studies of CYT-6091, a novel PEGylated colloidal gold-rhTNF nanomedicine. Clin Cancer Res. 2010;16(24):6139–49.

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  75. Kharlamov AN, Tyurnina AE, Veselova VS, Kovtun OP, Shur VY, Gabinsky JL. Silica-gold nanoparticles for atheroprotective management of plaques: results of the NANOM-FIM trial. Nanoscale. 2015;7(17):8003–15.

    CAS  Article  PubMed  Google Scholar 

  76. Marill J, Anesary NM, Zhang P, Vivet S, Borghi E, Levy L, et al. Hafnium oxide nanoparticles: toward an in vitro predictive biological effect? Radiat Oncol. 2014;9(1):150.

    Article  PubMed  PubMed Central  Google Scholar 

  77. Pottier A, Borghi E, Levy L. New use of metals as nanosized radioenhancers. Anticancer Res. 2014;34(1B):443–53.

    CAS  PubMed  Google Scholar 

  78. Phillips E, Penate-Medina O, Zanzonico PB, Carvajal RD, Mohan P, Ye YP, et al. Clinical translation of an ultrasmall inorganic optical-PET imaging nanoparticle probe. Sci Transl Med. 2014;6(260).

  79. Junghanns J-UAH, Müller RH. Nanocrystal technology, drug delivery and clinical applications. Int J Nanomedicine. 2008;3(3):295–309.

    CAS  PubMed  PubMed Central  Google Scholar 

  80. Shegokar R, Müller RH. Nanocrystals: industrially feasible multifunctional formulation technology for poorly soluble actives. Int J Pharm. 2010;399(1):129–39.

    CAS  Article  PubMed  Google Scholar 

  81. Möschwitzer J, Müller RH. New method for the effective production of ultrafine drug nanocrystals. J Nanosci Nanotechnol. 2006;6(9–10):3145–53.

    Article  PubMed  Google Scholar 

  82. Sirolimus: AY 22989, NSC 226080, NSC 606698, Rapamycin, Rapamune. Drugs in R & D. 1999;1(1):100–7.

  83. Almeida JP, Chen AL, Foster A, Drezek R. In vivo biodistribution of nanoparticles. Nanomedicine (London, England). 2011;6(5):815–35.

    CAS  Article  Google Scholar 

  84. Alexis F, Pridgen E, Molnar LK, Farokhzad OC. Factors affecting the clearance and biodistribution of polymeric nanoparticles. Mol Pharmaceut. 2008;5(4):505–15.

    CAS  Article  Google Scholar 

  85. Li S-D, Huang L. Pharmacokinetics and biodistribution of nanoparticles. Mol Pharmaceut. 2008;5(4):496–504.

    CAS  Article  Google Scholar 

  86. Blanco E, Shen H, Ferrari M. Principles of nanoparticle design for overcoming biological barriers to drug delivery. Nat Biotechnol. 2015;33(9):941–51.

    CAS  Article  PubMed  Google Scholar 

  87. Kendall M, Lynch I. Long-term monitoring for nanomedicine implants and drugs. Nat Nanotechnol. 2016;11(3):206–10.

    CAS  Article  PubMed  Google Scholar 

  88. Wang Y-XJ. Superparamagnetic iron oxide based MRI contrast agents: current status of clinical application. Quant Imaging Med Surg. 2011;1(1):35–40.

    PubMed  PubMed Central  Google Scholar 

  89. Stylianopoulos T, Jain RK. Design considerations for nanotherapeutics in oncology. Nanomed-Nanotechnol Biol Med. 2015;11(8):1893–907.

    CAS  Article  Google Scholar 

  90. Senzer N, Nemunaitis J, Nemunaitis D, Bedell C, Edelman G, Barve M, et al. Phase I study of a systemically delivered p53 nanoparticle in advanced solid tumors. Mol Ther. 2013;21(5):1096–103.

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  91. Draz MS, Fang BA, Zhang P, Hu Z, Gu S, Weng KC, et al. Nanoparticle-mediated systemic delivery of sirna for treatment of cancers and viral infections. Theranostics. 2014;4(9):872–92.

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  92. Mura S, Couvreur P. Nanotheranostics for personalized medicine. Adv Drug Deliv Rev. 2012;64(13):1394–416.

    CAS  Article  PubMed  Google Scholar 

  93. Thurecht KJ, Blakey I, Peng H, Squires O, Hsu S, Alexander C, et al. Functional hyperbranched polymers: toward targeted in vivo F-19 magnetic resonance imaging using designed macromolecules. J Am Chem Soc. 2010;132(15):5336−+.

    Article  PubMed  Google Scholar 

  94. Yildirimer L, Thanh NTK, Loizidou M, Seifalian AM. Toxicological considerations of clinically applicable nanoparticles. Nano Today. 2011;6(6):585–607.

    CAS  Article  PubMed  PubMed Central  Google Scholar 

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ACKNOWLEDGMENTS AND DISCLOSURES

We acknowledge funding from the National Health and Medical Research Council (APP1099231 KJT), the Australian Research Council (FT110100284, DP140100951 (KJT), DE130100800 (SRC)), National Breast Cancer Foundation (NC-14-037), and Centre of Excellence in Convergent BioNano Science and Technology (CE140100036 (SRC, KJT)) and thank the Ochsner Clinical School of New Orleans, LA (DPB).

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Correspondence to Simon R. Corrie.

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Bobo, D., Robinson, K.J., Islam, J. et al. Nanoparticle-Based Medicines: A Review of FDA-Approved Materials and Clinical Trials to Date. Pharm Res 33, 2373–2387 (2016). https://doi.org/10.1007/s11095-016-1958-5

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  • DOI: https://doi.org/10.1007/s11095-016-1958-5

KEY WORDS

  • clinical trials
  • FDA
  • nanomedicine
  • nanoparticles
  • nanopharmaceuticals
  • nanotherpeutics