Nanomedicine: is it lost in translation?

By the end of 2017 more than 200,000 scientific research articles had been published about nanomedicine. Out of this vast number only a few of the reported nanoconstructs reached clinical trials for various applications, including the diagnosis and treatment of several cancers, and the treatment of infections and other non-cancerous diseases. 30 years after the pioneering work in this field of research, the low product yield at the end of research pipeline leads to a question that is asked by many: 'had nanomedicine been lost in translation?' In this review, we will discuss the landscape of nanomedicine regarding cancer treatment and miscellaneous applications as well as some obstacles toward full utilization of this powerful therapeutic tool and suggest a few solutions to improve the current translational value of nanomedicine research.

[1]  P. L. McCormack,et al.  Methoxy Polyethylene Glycol-Epoetin Beta , 2012, Drugs.

[2]  R. López-Vélez,et al.  Drug resistance and treatment failure in leishmaniasis: A 21st century challenge , 2017, PLoS neglected tropical diseases.

[3]  F. Granucci,et al.  Drug nanocarriers to treat autoimmunity and chronic inflammatory diseases. , 2017, Seminars in immunology.

[4]  R. Duncan Polymer therapeutics at a crossroads? Finding the path for improved translation in the twenty-first century , 2017, Journal of drug targeting.

[5]  Yichao Chen,et al.  Doxorubicin delivered by a redox‐responsive dasatinib‐containing polymeric prodrug carrier for combination therapy , 2017, Journal of controlled release : official journal of the Controlled Release Society.

[6]  Jonathan Wang,et al.  Peptide and antibody ligands for renal targeting: nanomedicine strategies for kidney disease. , 2017, Biomaterials science.

[7]  L. Shao,et al.  The antimicrobial activity of nanoparticles: present situation and prospects for the future , 2017, International journal of nanomedicine.

[8]  Shaobing Zhou,et al.  Codelivery of a π–π Stacked Dual Anticancer Drug Combination with Nanocarriers for Overcoming Multidrug Resistance and Tumor Metastasis , 2016 .

[9]  R. S. Huang,et al.  Performance of the Verigene® enteric pathogens test, Biofire FilmArray™ gastrointestinal panel and Luminex xTAG® gastrointestinal pathogen panel for detection of common enteric pathogens. , 2016, Diagnostic microbiology and infectious disease.

[10]  O. Farokhzad,et al.  Nanomedicines for renal disease: current status and future applications , 2016, Nature Reviews Nephrology.

[11]  R. Harrison,et al.  Phase II and phase III failures: 2013–2015 , 2016, Nature Reviews Drug Discovery.

[12]  K. Sanyal,et al.  Chitosan Derivatives Active against Multidrug-Resistant Bacteria and Pathogenic Fungi: In Vivo Evaluation as Topical Antimicrobials. , 2016, Molecular pharmaceutics.

[13]  A. Garg,et al.  The efficacy and safety of sevelamer and lanthanum versus calcium-containing and iron-based binders in treating hyperphosphatemia in patients with chronic kidney disease: a systematic review and meta-analysis , 2016, Nephrology, dialysis, transplantation : official publication of the European Dialysis and Transplant Association - European Renal Association.

[14]  Marc Bickle,et al.  Screening out irrelevant cell-based models of disease , 2016, Nature Reviews Drug Discovery.

[15]  K. Thurecht,et al.  Nanoparticle-Based Medicines: A Review of FDA-Approved Materials and Clinical Trials to Date , 2016, Pharmaceutical Research.

[16]  N. Gu,et al.  The Smart Drug Delivery System and Its Clinical Potential , 2016, Theranostics.

[17]  A. J. Tavares,et al.  Analysis of nanoparticle delivery to tumours , 2016 .

[18]  D. Irvine Materializing the future of vaccines and immunotherapy , 2016 .

[19]  S. Mehr,et al.  The Latest Innovations in the Drug Pipeline for Multiple Sclerosis. , 2015, American health & drug benefits.

[20]  D. Irvine,et al.  Synthetic Nanoparticles for Vaccines and Immunotherapy. , 2015, Chemical reviews.

[21]  P. Turecek,et al.  Safety of PEGylated recombinant human full‐length coagulation factor VIII (BAX 855) in the overall context of PEG and PEG conjugates , 2015, Haemophilia : the official journal of the World Federation of Hemophilia.

[22]  S. Gordon,et al.  From the Reticuloendothelial to Mononuclear Phagocyte System – The Unaccounted Years , 2015, Front. Immunol..

[23]  I. Cockburn,et al.  The Economics of Reproducibility in Preclinical Research , 2015, PLoS biology.

[24]  M. Gharagozloo,et al.  Therapeutic applications of nanomedicine in autoimmune diseases: from immunosuppression to tolerance induction. , 2015, Nanomedicine : nanotechnology, biology, and medicine.

[25]  C. English,et al.  New FDA-Approved Disease-Modifying Therapies for Multiple Sclerosis. , 2015, Clinical therapeutics.

[26]  L. Spruce,et al.  Clinical Issues‐March 2015 , 2015 .

[27]  L. Freedman,et al.  The Impact of Preclinical Irreproducibility on Drug Development , 2015, Clinical pharmacology and therapeutics.

[28]  Joseph W. Nichols,et al.  EPR: Evidence and fallacy. , 2014, Journal of controlled release : official journal of the Controlled Release Society.

[29]  H. Young,et al.  Interferons: Success in anti-viral immunotherapy. , 2014, Cytokine & growth factor reviews.

[30]  Robert Langer,et al.  Nanomedicine in the Management of Microbial Infection - Overview and Perspectives. , 2014, Nano today.

[31]  Lawrence X. Yu,et al.  Pharmaceutical characterization and thermodynamic stability assessment of a colloidal iron drug product: iron sucrose. , 2014, International journal of pharmaceutics.

[32]  F. Liu,et al.  Combinational Delivery of Hydrophobic and Hydrophilic Anticancer Drugs in Single Nanoemulsions To Treat MDR in Cancer , 2014, Molecular pharmaceutics.

[33]  Hongjun Wang,et al.  Tissue regeneration : where nano-structure meets biology , 2014 .

[34]  Xuesi Chen,et al.  Anti-tumor efficacy of c(RGDfK)-decorated polypeptide-based micelles co-loaded with docetaxel and cisplatin. , 2014, Biomaterials.

[35]  F. Collins,et al.  Policy: NIH plans to enhance reproducibility , 2014, Nature.

[36]  D. Grainger,et al.  Modulation of the foreign body response to implanted sensor models through device-based delivery of the tyrosine kinase inhibitor, masitinib. , 2013, Biomaterials.

[37]  T. Ishida,et al.  The accelerated blood clearance (ABC) phenomenon: clinical challenge and approaches to manage. , 2013, Journal of controlled release : official journal of the Controlled Release Society.

[38]  D. Crommelin,et al.  Towards more effective advanced drug delivery systems. , 2013, International journal of pharmaceutics.

[39]  Albert Duschl,et al.  Interaction of nanoparticles with proteins: relation to bio-reactivity of the nanoparticle , 2013, Journal of Nanobiotechnology.

[40]  R. Mumper,et al.  A critical review of lipid-based nanoparticles for taxane delivery. , 2013, Cancer letters.

[41]  Andrew Z. Wang,et al.  Preclinical evaluation of Genexol-PM, a nanoparticle formulation of paclitaxel, as a novel radiosensitizer for the treatment of non-small cell lung cancer. , 2013, International journal of radiation oncology, biology, physics.

[42]  Ralph Weissleder,et al.  Polymeric Nanoparticle PET/MR Imaging Allows Macrophage Detection in Atherosclerotic Plaques , 2013, Circulation research.

[43]  K. Greish,et al.  Anticancer nanomedicine and tumor vascular permeability; Where is the missing link? , 2012, Journal of controlled release : official journal of the Controlled Release Society.

[44]  X. Jing,et al.  Co-delivery of daunomycin and oxaliplatin by biodegradable polymers for safer and more efficacious combination therapy. , 2012, Journal of controlled release : official journal of the Controlled Release Society.

[45]  E. Tamm,et al.  Kidney podocytes as specific targets for cyclo(RGDfC)-modified nanoparticles. , 2012, Small.

[46]  R. Wortmann,et al.  Latest evidence on gout management: what the clinician needs to know , 2012, Therapeutic advances in chronic disease.

[47]  Morteza Mahmoudi,et al.  Antibacterial properties of nanoparticles. , 2012, Trends in biotechnology.

[48]  Nicolas Anton,et al.  Inorganic Nanoparticles Based Contrast Agents for X‐ray Computed Tomography , 2012, Advanced healthcare materials.

[49]  Lehui Lu,et al.  Hybrid BaYbF5 Nanoparticles: Novel Binary Contrast Agent for High‐Resolution in Vivo X‐ray Computed Tomography Angiography , 2012, Advanced healthcare materials.

[50]  Y. Barenholz Doxil®--the first FDA-approved nano-drug: lessons learned. , 2012, Journal of controlled release : official journal of the Controlled Release Society.

[51]  Khaled Greish,et al.  Enhanced permeability and retention effect for selective targeting of anticancer nanomedicine: are we there yet? , 2012, Drug discovery today. Technologies.

[52]  C. Begley,et al.  Drug development: Raise standards for preclinical cancer research , 2012, Nature.

[53]  N. Desai Challenges in Development of Nanoparticle-Based Therapeutics , 2012, The AAPS Journal.

[54]  M. Banach,et al.  Ferumoxytol: a new era of iron deficiency anemia treatment for patients with chronic kidney disease. , 2011, Journal of nephrology.

[55]  D. Gianolio,et al.  (Bio)polymeric Hydrogels as Therapeutic Agents , 2011 .

[56]  S. Kaul,et al.  Fibrates in the treatment of dyslipidemias--time for a reassessment. , 2011, The New England journal of medicine.

[57]  Kinam Park,et al.  Targeted drug delivery to tumors: myths, reality and possibility. , 2011, Journal of controlled release : official journal of the Controlled Release Society.

[58]  Dong Soo Lee,et al.  Tumor targeting and imaging using cyclic RGD-PEGylated gold nanoparticle probes with directly conjugated iodine-125. , 2011, Small.

[59]  A. Baas,et al.  FDA-approved poly(ethylene glycol)–protein conjugate drugs , 2011 .

[60]  J. Kolitz,et al.  First-in-man study of CPX-351: a liposomal carrier containing cytarabine and daunorubicin in a fixed 5:1 molar ratio for the treatment of relapsed and refractory acute myeloid leukemia. , 2011, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[61]  R. Hargreaves,et al.  Development of aprepitant, the first neurokinin‐1 receptor antagonist for the prevention of chemotherapy‐induced nausea and vomiting , 2011, Annals of the New York Academy of Sciences.

[62]  W. Chui,et al.  Nanoparticulate Delivery System Targeted to Tumor Neovasculature for Combined Anticancer and Antiangiogenesis Therapy , 2011, Pharmaceutical Research.

[63]  Hisataka Kobayashi,et al.  In vivo molecular imaging using nanomaterials: General in vivo characteristics of nano-sized reagents and applications for cancer diagnosis (Review) , 2010, Molecular membrane biology.

[64]  Ick Chan Kwon,et al.  Tumor-homing multifunctional nanoparticles for cancer theragnosis: Simultaneous diagnosis, drug delivery, and therapeutic monitoring. , 2010, Journal of Controlled Release.

[65]  Y. Hata,et al.  Antiangiogenic drugs in the management of ocular diseases: Focus on antivascular endothelial growth factor , 2010, Clinical ophthalmology.

[66]  Ick Chan Kwon,et al.  Nanobubbles from gas-generating polymeric nanoparticles: ultrasound imaging of living subjects. , 2010, Angewandte Chemie.

[67]  P. Lu,et al.  Therapeutic Antibodies in Clinical Use and Leading Clinical Candidates , 2009 .

[68]  H. Maeda,et al.  Elevating blood pressure as a strategy to increase tumor-targeted delivery of macromolecular drug SMANCS: cases of advanced solid tumors. , 2009, Japanese journal of clinical oncology.

[69]  P. Meyers Muramyl tripeptide (mifamurtide) for the treatment of osteosarcoma , 2009, Expert review of anticancer therapy.

[70]  C. Kratochvil,et al.  Review of ADHD pharmacotherapies: advantages, disadvantages, and clinical pearls. , 2009, Journal of the American Academy of Child and Adolescent Psychiatry.

[71]  Gordon B. Mills,et al.  Derailed endocytosis: an emerging feature of cancer , 2008, Nature Reviews Cancer.

[72]  M. Shepherd,et al.  Extended-release, once-daily morphine (Avinza) for the treatment of chronic nonmalignant pain: effect on pain, depressive symptoms, and cognition. , 2008, Pain medicine.

[73]  Mark E. Davis,et al.  Nanoparticle therapeutics: an emerging treatment modality for cancer , 2008, Nature Reviews Drug Discovery.

[74]  Douglas A Christensen,et al.  Drug-loaded nano/microbubbles for combining ultrasonography and targeted chemotherapy. , 2008, Ultrasonics.

[75]  L. Lang FDA approves Cimzia to treat Crohn's disease. , 2008, Gastroenterology.

[76]  J. Adler-Moore,et al.  Amphotericin B lipid preparations: what are the differences? , 2008, Clinical microbiology and infection : the official publication of the European Society of Clinical Microbiology and Infectious Diseases.

[77]  Mauro Ferrari,et al.  Seven challenges for nanomedicine. , 2008, Nature nanotechnology.

[78]  Gerhard Ziemer,et al.  CELL-SELEX: Novel Perspectives of Aptamer-Based Therapeutics , 2008, International journal of molecular sciences.

[79]  Taro Shimizu,et al.  PEGylated liposomes elicit an anti-PEG IgM response in a T cell-independent manner. , 2007, Journal of controlled release : official journal of the Controlled Release Society.

[80]  M. Bawendi,et al.  Renal clearance of quantum dots , 2007, Nature Biotechnology.

[81]  H. Nasrallah,et al.  Paliperidone: a new extended-release oral atypical antipsychotic , 2007, Expert opinion on pharmacotherapy.

[82]  P. Keegan,et al.  FDA drug approval summary: pegaspargase (oncaspar) for the first-line treatment of children with acute lymphoblastic leukemia (ALL). , 2007, The oncologist.

[83]  D. Bassi,et al.  Carcinogen‐Induced Animal Models of Head and Neck Squamous Cell Carcinoma , 2007, Current protocols in pharmacology.

[84]  V. Torchilin Targeted pharmaceutical nanocarriers for cancer therapy and imaging , 2007, The AAPS Journal.

[85]  S. Levy,et al.  Molecular Mechanisms of Antibacterial Multidrug Resistance , 2007, Cell.

[86]  Wolfhard Semmler,et al.  Specific targeting of tumor angiogenesis by RGD-conjugated ultrasmall superparamagnetic iron oxide particles using a clinical 1.5-T magnetic resonance scanner. , 2007, Cancer research.

[87]  M. Schuster,et al.  Megestrol acetate in cachexia and anorexia , 2006, International journal of nanomedicine.

[88]  T. Ishida,et al.  Spleen plays an important role in the induction of accelerated blood clearance of PEGylated liposomes. , 2006, Journal of controlled release : official journal of the Controlled Release Society.

[89]  L. Tei,et al.  Magnetic resonance visualization of tumor angiogenesis by targeting neural cell adhesion molecules with the highly sensitive gadolinium-loaded apoferritin probe. , 2006, Cancer research.

[90]  C. Sharma,et al.  Nanoceramic Matrices: Biomedical Applications , 2006 .

[91]  H. Harputluoglu,et al.  Albumin-Bound Paclitaxel, ABI-007 May Show Better Efficacy than Paclitaxel in Basal-Like Breast Cancers: Association Between Caveolin-1 Expression and ABI-007 , 2006, Breast Cancer Research and Treatment.

[92]  Jan Grimm,et al.  An X-ray computed tomography imaging agent based on long-circulating bismuth sulphide nanoparticles , 2006, Nature materials.

[93]  M. Dewhirst,et al.  Targeted bioavailability of drugs by triggered release from liposomes , 2006 .

[94]  Brij M Moudgil,et al.  Fluorescent Nanoparticle Probes for Cancer Imaging , 2005, Technology in cancer research & treatment.

[95]  C. Hartrick,et al.  Extended‐Release Epidural Morphine (DepoDur™): An Old Drug with a New Profile , 2005, Pain practice : the official journal of World Institute of Pain.

[96]  R. Arnon,et al.  Mechanism of action of glatiramer acetate in multiple sclerosis and its potential for the development of new applications , 2004, Proceedings of the National Academy of Sciences of the United States of America.

[97]  M. Knopp,et al.  Polyamine dendrimer‐based MRI contrast agents for functional kidney imaging to diagnose acute renal failure , 2004, Journal of magnetic resonance imaging : JMRI.

[98]  S. Nie,et al.  In vivo cancer targeting and imaging with semiconductor quantum dots , 2004, Nature Biotechnology.

[99]  O. Westphal,et al.  Paul Ehrlich--in search of the magic bullet. , 2004, Microbes and infection.

[100]  D. Hussar New drugs of 2003. , 2004, Journal of the American Pharmacists Association : JAPhA.

[101]  Liron Levy,et al.  Trends in the development of chiral drugs. , 2004, Drug discovery today.

[102]  J. Camardo,et al.  The Rapamune era of immunosuppression 2003: the journey from the laboratory to clinical transplantation. , 2003, Transplantation proceedings.

[103]  S. Dhib-jalbut,et al.  Glatiramer acetate (Copaxone) therapy for multiple sclerosis. , 2003, Pharmacology & therapeutics.

[104]  O. Sartor Eligard: leuprolide acetate in a novel sustained-release delivery system. , 2003, Urology.

[105]  Amy L. Ladd,et al.  Bone graft substitutes , 2002 .

[106]  S M Moghimi,et al.  Long-circulating and target-specific nanoparticles: theory to practice. , 2001, Pharmacological reviews.

[107]  S. Fishbane,et al.  The Comparative Safety of Intravenous Iron Dextran, Iron Saccharate, and Sodium Ferric Gluconate , 2000, Seminars in dialysis.

[108]  G. Kearns,et al.  Lipid amphotericin preparations. , 2000, The Pediatric infectious disease journal.

[109]  R K Jain,et al.  Openings between defective endothelial cells explain tumor vessel leakiness. , 2000, The American journal of pathology.

[110]  W. Oyen,et al.  Accelerated blood clearance and altered biodistribution of repeated injections of sterically stabilized liposomes. , 2000, The Journal of pharmacology and experimental therapeutics.

[111]  F. Yuan,et al.  Transvascular drug delivery in solid tumors. , 1998, Seminars in radiation oncology.

[112]  M. S. Kaplan Tizanidine: Another Tool in the Management of Spasticity , 1997 .

[113]  M. Hershfield,et al.  PEG-ADA replacement therapy for adenosine deaminase deficiency: an update after 8.5 years. , 1995, Clinical immunology and immunopathology.

[114]  H. Maeda,et al.  A new concept for macromolecular therapeutics in cancer chemotherapy: mechanism of tumoritropic accumulation of proteins and the antitumor agent smancs. , 1986, Cancer research.

[115]  H. Maeda,et al.  Use of oily contrast medium for selective drug targeting to tumor: enhanced therapeutic effect and X-ray image. , 1984, Cancer research.

[116]  H. Peterson,et al.  Experimental studies on the uptake and rentention of labelled proteins in a rat tumour. , 1973, European journal of cancer.

[117]  J. Folkman Tumor angiogenesis: therapeutic implications. , 1971, The New England journal of medicine.

[118]  J. Folkman,et al.  ISOLATION OF A TUMOR FACTOR RESPONSIBLE FOR ANGIOGENESIS , 1971, The Journal of experimental medicine.

[119]  Fiona B Wertheimer,et al.  Evolution of surfactant therapy for respiratory distress syndrome: past, present, and future , 2017, Pediatric Research.

[120]  J. Verma,et al.  Inorganic nanoparticles for the theranostics of cancer , 2015 .

[121]  B. Ruggeri,et al.  Animal models of disease: pre-clinical animal models of cancer and their applications and utility in drug discovery. , 2014, Biochemical pharmacology.

[122]  J. Reid,et al.  Antiparkinsonian Drugs: Pharmacological and Therapeutic Aspects , 2012, Drugs.

[123]  Marit D. Moen,et al.  Liposomal Amphotericin B , 2012, Drugs.

[124]  M. Camacho-López,et al.  (99m)Tc-labelled gold nanoparticles capped with HYNIC-peptide/mannose for sentinel lymph node detection. , 2011, Nuclear medicine and biology.

[125]  M. Muñoz,et al.  Intravenous iron therapy: how far have we come? , 2011, Revista brasileira de hematologia e hemoterapia.

[126]  Khaled Greish,et al.  Enhanced permeability and retention (EPR) effect for anticancer nanomedicine drug targeting. , 2010, Methods in molecular biology.

[127]  Lawrence Mayer,et al.  In vivo maintenance of synergistic cytarabine:daunorubicin ratios greatly enhances therapeutic efficacy. , 2009, Leukemia research.

[128]  E. Wisse,et al.  The size of endothelial fenestrae in human liver sinusoids: implications for hepatocyte-directed gene transfer , 2008, Gene Therapy.

[129]  V. Torchilin,et al.  CT visualization of blood pool in rats by using long-circulating, iodine-containing micelles. , 1999, Academic radiology.

[130]  A. Meyerhoff U.S. Food and Drug Administration approval of AmBisome (liposomal amphotericin B) for treatment of visceral leishmaniasis. , 1999, Clinical infectious diseases : an official publication of the Infectious Diseases Society of America.

[131]  A. Sachse,et al.  Biodistribution and Ct-Imaging Characteristics of Iopromide-Carrying Liposomes in Rats , 1996 .