Mechanisms and Barriers in Cancer Nanomedicine: Addressing Challenges, Looking for Solutions.

Remarkable progress has recently been made in the synthesis and characterization of engineered nanoparticles for imaging and treatment of cancers, resulting in several promising candidates in clinical trials. Despite these advances, clinical applications of nanoparticle-based therapeutic/imaging agents remain limited by biological, immunological, and translational barriers. In order to overcome the existing status quo in drug delivery, there is a need for open and frank discussion in the nanomedicine community on what is needed to make qualitative leaps toward translation. In this Nano Focus, we present the main discussion topics and conclusions from a recent workshop: "Mechanisms and Barriers in Nanomedicine". The focus of this informal meeting was on biological, toxicological, immunological, and translational aspects of nanomedicine and approaches to move the field forward productively. We believe that these topics reflect the most important issues in cancer nanomedicine.

[1]  H. Hochster,et al.  Phase II study of liposomal cisplatin (SPI-77) in platinum-sensitive recurrences of ovarian cancer. , 2010, Anticancer research.

[2]  S M Moghimi,et al.  Cancer nanomedicine and the complement system activation paradigm: anaphylaxis and tumour growth. , 2014, Journal of controlled release : official journal of the Controlled Release Society.

[3]  Mark E. Davis,et al.  Mechanism of active targeting in solid tumors with transferrin-containing gold nanoparticles , 2009, Proceedings of the National Academy of Sciences.

[4]  S. Moghimi,et al.  Just so stories: the random acts of anti-cancer nanomedicine performance. , 2014, Nanomedicine : nanotechnology, biology, and medicine.

[5]  I. Alferiev,et al.  Nanoparticle-mediated delivery of a rapidly activatable prodrug of SN-38 for neuroblastoma therapy. , 2015, Biomaterials.

[6]  L. Pagliaro,et al.  Photothermal therapy using gold nanorods and near-infrared light in a murine melanoma model increases survival and decreases tumor volume , 2014 .

[7]  Marina A. Dobrovolskaia,et al.  Common pitfalls in nanotechnology: lessons learned from NCI's Nanotechnology Characterization Laboratory. , 2013, Integrative biology : quantitative biosciences from nano to macro.

[8]  K. Alitalo,et al.  Lymphatic vessels regulate immune microenvironments in human and murine melanoma. , 2016, The Journal of clinical investigation.

[9]  Erkki Ruoslahti,et al.  Tissue-penetrating delivery of compounds and nanoparticles into tumors. , 2009, Cancer cell.

[10]  M. Ferrari,et al.  Redirecting Transport of Nanoparticle Albumin-Bound Paclitaxel to Macrophages Enhances Therapeutic Efficacy against Liver Metastases. , 2016, Cancer research.

[11]  James E Bear,et al.  Nanoparticle clearance is governed by Th1/Th2 immunity and strain background. , 2013, The Journal of clinical investigation.

[12]  F. Kiessling,et al.  Drug targeting to tumors: principles, pitfalls and (pre-) clinical progress. , 2012, Journal of controlled release : official journal of the Controlled Release Society.

[13]  Hamidreza Ghandehari,et al.  High intensity focused ultrasound hyperthermia for enhanced macromolecular delivery. , 2016, Journal of controlled release : official journal of the Controlled Release Society.

[14]  S. Goldberg,et al.  Therapeutic Efficacy of Combining PEGylated Liposomal Doxorubicin and Radiofrequency (RF) Ablation: Comparison between Slow-Drug-Releasing, Non-Thermosensitive and Fast-Drug-Releasing, Thermosensitive Nano-Liposomes , 2014, PloS one.

[15]  Tracy K. Pettinger,et al.  Nanopharmaceuticals (part 1): products on the market , 2014, International journal of nanomedicine.

[16]  M. Machluf,et al.  Nanoghosts as a Novel Natural Nonviral Gene Delivery Platform Safely Targeting Multiple Cancers. , 2016, Nano letters.

[17]  Mauro Ferrari,et al.  Enhanced performance of macrophage-encapsulated nanoparticle albumin-bound-paclitaxel in hypo-perfused cancer lesions. , 2016, Nanoscale.

[18]  F M Muggia,et al.  Complement activation following first exposure to pegylated liposomal doxorubicin (Doxil): possible role in hypersensitivity reactions. , 2003, Annals of oncology : official journal of the European Society for Medical Oncology.

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

[20]  Ashley M. Laughney,et al.  Predicting therapeutic nanomedicine efficacy using a companion magnetic resonance imaging nanoparticle , 2015, Science Translational Medicine.

[21]  A. Gabizon,et al.  Liposome promotion of tumor growth is associated with angiogenesis and inhibition of antitumor immune responses. , 2015, Nanomedicine : nanotechnology, biology, and medicine.

[22]  Samir Mitragotri,et al.  Impact of particle elasticity on particle‐based drug delivery systems☆ , 2017, Advanced drug delivery reviews.

[23]  Jaehong Key,et al.  Soft Discoidal Polymeric Nanoconstructs Resist Macrophage Uptake and Enhance Vascular Targeting in Tumors. , 2015, ACS nano.

[24]  Ji-Ho Park,et al.  Liposome-based engineering of cells to package hydrophobic compounds in membrane vesicles for tumor penetration. , 2015, Nano letters.

[25]  M. Dobrovolskaia,et al.  Endotoxin and Engineered Nanomaterials , 2013 .

[26]  Janos Szebeni,et al.  Complement activation-related pseudoallergy: a new class of drug-induced acute immune toxicity. , 2005, Toxicology.

[27]  A. Gabizon,et al.  New insights and evolving role of pegylated liposomal doxorubicin in cancer therapy. , 2016, Drug resistance updates : reviews and commentaries in antimicrobial and anticancer chemotherapy.

[28]  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.

[29]  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.

[30]  V. M. Holers,et al.  Modulatory Role of Surface Coating of Superparamagnetic Iron Oxide Nanoworms in Complement Opsonization and Leukocyte Uptake. , 2015, ACS nano.

[31]  D. Peer,et al.  Immunomodulation of hematological malignancies using oligonucleotides based-nanomedicines. , 2016, Journal of controlled release : official journal of the Controlled Release Society.

[32]  Mauro Ferrari,et al.  Intravascular Delivery of Particulate Systems: Does Geometry Really Matter? , 2008, Pharmaceutical Research.

[33]  Morteza Mahmoudi,et al.  Iron oxide nanoparticles inhibit tumour growth by inducing pro-inflammatory macrophage polarization in tumour tissues. , 2016, Nature nanotechnology.

[34]  A. Gabizon,et al.  Preclinical Evaluation of Promitil, a Radiation-Responsive Liposomal Formulation of Mitomycin C Prodrug, in Chemoradiotherapy. , 2016, International Journal of Radiation Oncology, Biology, Physics.

[35]  Yechezkel Barenholz,et al.  In vitro experiments showing enhanced release of doxorubicin from Doxil® in the presence of ammonia may explain drug release at tumor site. , 2015, Nanomedicine : nanotechnology, biology, and medicine.

[36]  R. Thorpe,et al.  Cytokine release assays for the prediction of therapeutic mAb safety in first-in man trials — Whole blood cytokine release assays are poorly predictive for TGN1412 cytokine storm , 2015, Journal of immunological methods.

[37]  S. Moein Moghimi,et al.  Nanomedicine and the complement paradigm. , 2013, Nanomedicine : nanotechnology, biology, and medicine.

[38]  Y. Barenholz,et al.  Coencapsulation of alendronate and doxorubicin in pegylated liposomes: a novel formulation for chemoimmunotherapy of cancer , 2016, Journal of drug targeting.

[39]  S. Alzghari,et al.  Meta-analysis of clinical and preclinical studies comparing the anticancer efficacy of liposomal versus conventional non-liposomal doxorubicin. , 2016, Journal of controlled release : official journal of the Controlled Release Society.

[40]  Mina J. Bissell,et al.  The perivascular niche regulates breast tumor dormancy , 2013, Nature Cell Biology.