Nanodiamond-mediated delivery of water-insoluble therapeutics.

A broad array of water-insoluble compounds has displayed therapeutically relevant properties toward a spectrum of medical and physiological disorders, including cancer and inflammation. However, the continued search for scalable, facile, and biocompatible routes toward mediating the dispersal of these compounds in water has limited their widespread application in medicine. Here we demonstrate a platform approach of water-dispersible, nanodiamond cluster-mediated interactions with several therapeutics to enhance their suspension in water with preserved functionality, thereby enabling novel treatment paradigms that were previously unrealized. These therapeutics include Purvalanol A, a highly promising compound for hepatocarcinoma (liver cancer) treatment, 4-hydroxytamoxifen (4-OHT), an emerging drug for the treatment of breast cancer, as well as dexamethasone, a clinically relevant anti-inflammatory that has addressed an entire spectrum of diseases that span complications from blood and brain cancers to rheumatic and renal disorders. Given the scalability of nanodiamond processing and functionalization, this novel approach serves as a facile, broadly impacting and significant route to translate water-insoluble compounds toward treatment-relevant scenarios.

[1]  Houjin Huang,et al.  Protein-mediated assembly of nanodiamond hydrogels into a biocompatible and biofunctional multilayer nanofilm. , 2008, ACS nano.

[2]  P. Pantazis Preclinical studies of water-insoluble camptothecin congeners: cytotoxicity, development of resistance, and combination treatments. , 1995, Clinical cancer research : an official journal of the American Association for Cancer Research.

[3]  R. Garrell,et al.  Surface-modified diamond nanoparticles as antigen delivery vehicles. , 1995, Bioconjugate chemistry.

[4]  J. Girault,et al.  Neoadjuvant percutaneous 4-hydroxytamoxifen decreases breast tumoral cell proliferation: a prospective controlled randomized study comparing three doses of 4-hydroxytamoxifen gel to oral tamoxifen. , 2005, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[5]  C K Redmond,et al.  Tamoxifen for prevention of breast cancer: report of the National Surgical Adjuvant Breast and Bowel Project P-1 Study. , 1999, Journal of the National Cancer Institute.

[6]  R Langer,et al.  New methods of drug delivery. , 1990, Science.

[7]  A. Krüger Hard and soft: biofunctionalized diamond. , 2006, Angewandte Chemie.

[8]  Saber M Hussain,et al.  Are diamond nanoparticles cytotoxic? , 2007, The journal of physical chemistry. B.

[9]  Stephan Marsch,et al.  Cell targeting by a generic receptor-targeted polymer nanocontainer platform. , 2005, Journal of controlled release : official journal of the Controlled Release Society.

[10]  A. Tward,et al.  Inhibition of CDK1 as a potential therapy for tumors over-expressing MYC , 2007, Nature Medicine.

[11]  F. May,et al.  Effects of tamoxifen and 4-hydroxytamoxifen on the pNR-1 and pNR-2 estrogen-regulated RNAs in human breast cancer cells. , 1987, The Journal of biological chemistry.

[12]  Erik Pierstorff,et al.  Active nanodiamond hydrogels for chemotherapeutic delivery. , 2007, Nano letters.

[13]  Huan-Cheng Chang,et al.  Adsorption and immobilization of cytochrome c on nanodiamonds. , 2004, Langmuir : the ACS journal of surfaces and colloids.

[14]  Lloyd M. Smith,et al.  DNA-modified nanocrystalline diamond thin-films as stable, biologically active substrates , 2002, Nature materials.

[15]  D. Gruen,et al.  Ultrananocrystalline diamond thin films functionalized with therapeutically active collagen networks. , 2009, The journal of physical chemistry. B.

[16]  J. Kohn,et al.  Hydrophobic drug delivery by self-assembling triblock copolymer-derived nanospheres. , 2005, Biomacromolecules.

[17]  Martin Stutzmann,et al.  Protein-modified nanocrystalline diamond thin films for biosensor applications , 2004, Nature materials.

[18]  F. Gouilleux,et al.  4-Hydroxytamoxifen Inhibits Proliferation of Multiple Myeloma Cells In vitro through Down-Regulation of c-Myc, Up-Regulation of p27Kip1, and Modulation of Bcl-2 Family Members , 2005, Clinical Cancer Research.

[19]  Omid C Farokhzad,et al.  Co‐Delivery of Hydrophobic and Hydrophilic Drugs from Nanoparticle–Aptamer Bioconjugates , 2007, ChemMedChem.

[20]  D. Gruen,et al.  Diamond nanowires and the insulator-metal transition in ultrananocrystalline diamond films , 2007 .

[21]  A. Graff,et al.  Virus-assisted loading of polymer nanocontainer , 2002, Proceedings of the National Academy of Sciences of the United States of America.

[22]  Yee Ying Tan,et al.  Using detonation nanodiamond for the specific capture of glycoproteins. , 2008, Analytical chemistry.

[23]  Stephan Marsch,et al.  Cell-specific integration of artificial organelles based on functionalized polymer vesicles. , 2008, Nano letters.

[24]  T. Deming,et al.  Methodologies for preparation of synthetic block copolypeptides: materials with future promise in drug delivery. , 2002, Advanced drug delivery reviews.

[25]  Dieter M. Gruen,et al.  NANOCRYSTALLINE DIAMOND FILMS1 , 1999 .

[26]  Andrea Zappe,et al.  Dynamics of diamond nanoparticles in solution and cells. , 2007, Nano letters.

[27]  Erik Pierstorff,et al.  Nanodiamond-embedded microfilm devices for localized chemotherapeutic elution. , 2008, ACS nano.

[28]  Robert Langer,et al.  Self-assembled lipid--polymer hybrid nanoparticles: a robust drug delivery platform. , 2008, ACS nano.

[29]  D. Zava,et al.  Estrogen receptor-mediated and cytotoxic effects of the antiestrogens tamoxifen and 4-hydroxytamoxifen. , 1984, Cancer research.

[30]  Huan-Cheng Chang,et al.  Bright fluorescent nanodiamonds: no photobleaching and low cytotoxicity. , 2005, Journal of the American Chemical Society.

[31]  Dennis E Discher,et al.  Polymeric worm micelles as nano-carriers for drug delivery , 2005, Nanotechnology.

[32]  M. Prato,et al.  Carbon nanotubes as nanomedicines: from toxicology to pharmacology. , 2006, Advanced drug delivery reviews.

[33]  S. Wise Nanocarriers as an emerging platform for cancer therapy , 2007 .

[34]  James Dignam,et al.  Tamoxifen in treatment of intraductal breast cancer: National Surgical Adjuvant Breast and Bowel Project B-24 randomised controlled trial , 1999, The Lancet.

[35]  E. Wagner,et al.  Design and gene delivery activity of modified polyethylenimines. , 2001, Advanced drug delivery reviews.

[36]  Valerii Yu. Dolmatov,et al.  Detonation synthesis ultradispersed diamonds: properties and applications , 2001 .

[37]  Zhuang Liu,et al.  PEGylated nanographene oxide for delivery of water-insoluble cancer drugs. , 2008, Journal of the American Chemical Society.

[38]  H. Dai,et al.  Carbon nanotubes as multifunctional biological transporters and near-infrared agents for selective cancer cell destruction. , 2005, Proceedings of the National Academy of Sciences of the United States of America.

[39]  T. Bettinger,et al.  Size reduction of galactosylated PEI/DNA complexes improves lectin-mediated gene transfer into hepatocytes. , 1999, Bioconjugate chemistry.

[40]  Y. Gogotsi,et al.  Wet chemistry route to hydrophobic blue fluorescent nanodiamond. , 2009, Journal of the American Chemical Society.

[41]  Alexey P. Puzyr,et al.  Nanodiamonds for biological investigations , 2004 .

[42]  M. Ozawa,et al.  Preparation and Behavior of Brownish, Clear Nanodiamond Colloids , 2007 .

[43]  J. Mester,et al.  Cellular effects of purvalanol A: A specific inhibitor of cyclin‐dependent kinase activities , 2002, International journal of cancer.

[44]  Chia-Liang Cheng,et al.  Biocompatible and detectable carboxylated nanodiamond on human cell , 2007 .

[45]  M. Ozawa,et al.  Unusually tight aggregation in detonation nanodiamond: Identification and disintegration , 2005 .