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.
This is a preview of subscription content, access via your institution.
Buy single article
Instant access to the full article PDF.
Price excludes VAT (USA)
Tax calculation will be finalised during checkout.
Chemotherapy containing cyclophosmphamide, doxorubicin, vincristine, and prednisolone
Chronic Kidney Disease
Critical micelle concentration
Cyclic arginine-glycine-aspartic acid
Enhanced permeability and retention
Investigational device exemption
Investigational New Drug
Molecularly targeted agents
Albumin bound nanoparticles
Nanotechnology Characterization Laboratory
New Drug Application
Poly (ethylene glycol)
Prostate-specific membrane antigen
Peripheral T-cell lymphomas
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.
Chaudhuri RG, Paria S. Core/Shell nanoparticles: classes, properties, synthesis mechanisms, characterization, and applications. Chem Rev. 2012;112(4):2373–433.
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.
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.
Elsabahy M, Wooley KL. Design of polymeric nanoparticles for biomedical delivery applications. Chem Soc Rev. 2012;41(7):2545–61.
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.
Tang F, Li L, Chen D. Mesoporous silica nanoparticles: synthesis, biocompatibility and drug delivery. Adv Mater. 2012;24(12):1504–34.
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.
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.
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.
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.
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.
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.
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.
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.
Duncan R, Sat YN. Tumour targeting by enhanced permeability and retention (EPR) effect. Ann Oncol. 1998;9:39.
Casi G, Neri D. Antibody–drug conjugates: basic concepts, examples and future perspectives. J Control Release. 2012;161(2):422–8.
Diamantis N, Banerji U. Antibody-drug conjugates—an emerging class of cancer treatment. Br J Cancer. 2016;114(4):362–7.
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.
Dobrovolskaia MA. Pre-clinical immunotoxicity studies of nanotechnology-formulated drugs: challenges, considerations and strategy. J Control Release. 2015;220:571–83.
Nanotechnology Characterization Laboratory: National Cancer Institute US National Institues of Health; 2016 [2/16/2016]. Available from: http://ncl.cancer.gov/.
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.
Registered Clinical Trial Database [Internet]. 2016 [cited 2/15/2016]. Available from: https://clinicaltrials.gov/.
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.
Svenson S. What nanomedicine in the clinic right now really forms nanoparticles? Wiley Interdisciplinary Reviews. Nanomed Nanobiotechnol. 2014;6(2):125–35.
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.
Cures P. Neglected disease research and development: is the global financial crisis changing R&D. London: Policy Cures; 2011.
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.
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.
Duncan R. Polymer therapeutics: Top 10 selling pharmaceuticals - What next? J Control Release. 2014;190:371–80.
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.
Alconcel SNS, Baas AS, Maynard HD. FDA-approved poly(ethylene glycol)-protein conjugate drugs. Polym Chem. 2011;2(7):1442–8.
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.
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.
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.
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.
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.
Berges R. Eligard (R): Pharmacokinetics, effect on testosterone and PSA levels and tolerability. Eur Urol Suppl. 2005;4(5):20–5.
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.
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.
Taylor DD, Gercel-Taylor C. MicroRNA signatures of tumor-derived exosomes as diagnostic biomarkers of ovarian cancer. Gynecol Oncol. 2008;110(1):13–21.
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).
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.
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.
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.
Bangham AD, Standish MM, Watkins JC. Diffusion of univalent ions across lamellae of swollen phospholipids. J Mol Biol. 1965;13(1):238.
Allen TM, Cullis PR. Liposomal drug delivery systems: from concept to clinical applications. Adv Drug Deliv Rev. 2013;65(1):36–48.
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.
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.
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.
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.
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.
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.
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.
May JP, Li S-D. Hyperthermia-induced drug targeting. Exp Opin Drug Deliv. 2013;10(4):511–27.
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.
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.
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.
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.
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.
Foss F. Clinical experience with Denileukin Diftitox (ONTAK). Semin Oncol. 2006;33(Supplement 3):11–6.
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.
Gordon EM, Hall FL. Rexin-G, a targeted genetic medicine for cancer. Expert Opin Biol Ther. 2010;10(5):819–32.
Salah EDTA, Bakr MM, Kamel HM, Abdel KM. Magnetite nanoparticles as a single dose treatment for iron deficiency anemia. Google Patents. 2010.
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.
Wang Y-XJ. Current status of superparamagnetic iron oxide contrast agents for liver magnetic resonance imaging. World J Gastroenterol. 2015;21(47):13400–2.
Thiesen B, Jordan A. Clinical applications of magnetic nanoparticles for hyperthermia. Int J Hyperther. 2008;24(6):467–74.
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.
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.
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.
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.
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.
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.
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.
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.
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.
Pottier A, Borghi E, Levy L. New use of metals as nanosized radioenhancers. Anticancer Res. 2014;34(1B):443–53.
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).
Junghanns J-UAH, Müller RH. Nanocrystal technology, drug delivery and clinical applications. Int J Nanomedicine. 2008;3(3):295–309.
Shegokar R, Müller RH. Nanocrystals: industrially feasible multifunctional formulation technology for poorly soluble actives. Int J Pharm. 2010;399(1):129–39.
Möschwitzer J, Müller RH. New method for the effective production of ultrafine drug nanocrystals. J Nanosci Nanotechnol. 2006;6(9–10):3145–53.
Sirolimus: AY 22989, NSC 226080, NSC 606698, Rapamycin, Rapamune. Drugs in R & D. 1999;1(1):100–7.
Almeida JP, Chen AL, Foster A, Drezek R. In vivo biodistribution of nanoparticles. Nanomedicine (London, England). 2011;6(5):815–35.
Alexis F, Pridgen E, Molnar LK, Farokhzad OC. Factors affecting the clearance and biodistribution of polymeric nanoparticles. Mol Pharmaceut. 2008;5(4):505–15.
Li S-D, Huang L. Pharmacokinetics and biodistribution of nanoparticles. Mol Pharmaceut. 2008;5(4):496–504.
Blanco E, Shen H, Ferrari M. Principles of nanoparticle design for overcoming biological barriers to drug delivery. Nat Biotechnol. 2015;33(9):941–51.
Kendall M, Lynch I. Long-term monitoring for nanomedicine implants and drugs. Nat Nanotechnol. 2016;11(3):206–10.
Wang Y-XJ. Superparamagnetic iron oxide based MRI contrast agents: current status of clinical application. Quant Imaging Med Surg. 2011;1(1):35–40.
Stylianopoulos T, Jain RK. Design considerations for nanotherapeutics in oncology. Nanomed-Nanotechnol Biol Med. 2015;11(8):1893–907.
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.
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.
Mura S, Couvreur P. Nanotheranostics for personalized medicine. Adv Drug Deliv Rev. 2012;64(13):1394–416.
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−+.
Yildirimer L, Thanh NTK, Loizidou M, Seifalian AM. Toxicological considerations of clinically applicable nanoparticles. Nano Today. 2011;6(6):585–607.
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).
Rights and permissions
About this article
Cite this article
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
- clinical trials