Facile biosynthesis, separation and conjugation of gold nanoparticles to doxorubicin

Particle shape and size determine the physicochemical and optoelectronic properties of nanoscale materials, including optical absorption, fluorescence, and electric and magnetic moments. It is thus desirable to be able to synthesize and separate various particle shapes and sizes. Biosynthesis using microorganisms has emerged as a more ecologically friendly, simpler, and more reproducible alternative to chemical synthesis of metal and semiconductor nanoparticles, allowing the generation of rare forms such as triangles. Here we show that the plant pathogenic fungus Helminthosporum solani, when incubated with an aqueous solution of chloroaurate ions, produces a diverse mixture of extracellular gold nanocrystals in the size range from 2 to 70 nm. A plurality are polydisperse spheres, but a significant number are homogeneously sized rods, triangles, pentagons, pyramids, and stars. The particles can be separated according to their size and shape by using a sucrose density gradient in a tabletop microcentrifuge, a novel and facile approach to nanocrystal purification. Conjugation to biomolecules can be performed without further processing, as illustrated with the smallest fraction of particles which were conjugated to the anti-cancer drug doxorubicin (Dox) and taken up readily into HEK293 cells. The cytotoxicity of the conjugates was comparable to that of an equivalent concentration of Dox.

[1]  Robert Langer,et al.  Quantum dot-aptamer conjugates for synchronous cancer imaging, therapy, and sensing of drug delivery based on bi-fluorescence resonance energy transfer. , 2007, Nano letters.

[2]  Fu-Ken Liu,et al.  Adding sodium dodecylsulfate to the running electrolyte enhances the separation of gold nanoparticles by capillary electrophoresis , 2004 .

[3]  Rajinder K. Gupta,et al.  Nanotechnology and Potential of Microorganisms , 2005, Critical reviews in biotechnology.

[4]  Feng Gao,et al.  The application of Fe3O4 nanoparticles in cancer research: a new strategy to inhibit drug resistance. , 2007, Journal of biomedical materials research. Part A.

[5]  Ji-Xin Cheng,et al.  Hyperthermic effects of gold nanorods on tumor cells. , 2007, Nanomedicine.

[6]  K. Yokoyama,et al.  The conjugation of amyloid beta protein on the gold colloidal nanoparticles’ surfaces , 2007 .

[7]  Yadong Yin,et al.  Colloidal nanocrystal synthesis and the organic–inorganic interface , 2005, Nature.

[8]  P. Couvreur,et al.  A new method to isolate polyalkylcyanoacrylate nanoparticle preparations. , 1995, Journal of drug targeting.

[9]  James E Hutchison,et al.  Rapid purification and size separation of gold nanoparticles via diafiltration. , 2006, Journal of the American Chemical Society.

[10]  David L. Carroll,et al.  Synthesis and Characterization of Truncated Triangular Silver Nanoplates , 2002 .

[11]  Ron C. Hardman A Toxicologic Review of Quantum Dots: Toxicity Depends on Physicochemical and Environmental Factors , 2005, Environmental health perspectives.

[12]  D. Yourtee,et al.  Oxidative mutagenesis of doxorubicin-Fe(III) complex. , 2001, Mutation research.

[13]  R. Rosenfeld,et al.  Deciphering the fluorescence signature of daunomycin and doxorubicin. , 1998, Biophysical chemistry.

[14]  Sangjin Park,et al.  Antibiofouling polymer-coated gold nanoparticles as a contrast agent for in vivo X-ray computed tomography imaging. , 2007 .

[15]  John C. Bischof,et al.  Enhancement of tumor thermal therapy using gold nanoparticle–assisted tumor necrosis factor-α delivery , 2006, Molecular Cancer Therapeutics.

[16]  A. Belcher,et al.  Bacterial biosynthesis of cadmium sulfide nanocrystals. , 2004, Chemistry & biology.

[17]  A. Alivisatos Perspectives on the Physical Chemistry of Semiconductor Nanocrystals , 1996 .

[18]  Hong Yuan,et al.  Improved cytotoxicity of doxorubicin by enhancing its nuclear delivery mediated via nanosized micelles , 2008, Nanotechnology.

[19]  W. Faulk,et al.  Transferrin conjugates of adriamycin are cytotoxic without intercalating nuclear DNA. , 1992, The Journal of biological chemistry.

[20]  Liberato Manna,et al.  Synthesis of Soluble and Processable Rod-, Arrow-, Teardrop-, and Tetrapod-Shaped CdSe Nanocrystals , 2000 .

[21]  K. Janes,et al.  Chitosan nanoparticles as delivery systems for doxorubicin. , 2001, Journal of controlled release : official journal of the Controlled Release Society.

[22]  M. El-Sayed,et al.  Some interesting properties of metals confined in time and nanometer space of different shapes. , 2001, Accounts of chemical research.

[23]  James R. Heath,et al.  Synthesis and Characterization of Hydrophobic, Organically-Soluble Gold Nanocrystals Functionalized with Primary Amines , 1996 .

[24]  Absar Ahmad,et al.  Sulfite reductase‐mediated synthesis of gold nanoparticles capped with phytochelatin , 2007, Biotechnology and applied biochemistry.

[25]  Sulabha K. Kulkarni,et al.  Nitrate reductase-mediated synthesis of silver nanoparticles from AgNO3 , 2007, Biotechnology Letters.

[26]  Igor L. Medintz,et al.  Quantum dot bioconjugates for imaging, labelling and sensing , 2005, Nature materials.

[27]  Mariekie Gericke,et al.  BIOLOGICAL SYNTHESIS OF METAL NANOPARTICLES , 2006 .

[28]  O. Shpilberg,et al.  Appraisal of the MTT-based Assay as a Useful Tool for Predicting Drug Chemosensitivity in Leukemia , 2003, Leukemia & lymphoma.

[29]  A. Henglein Chemical and optical properties of small metal particles in aqueous solution , 1993 .

[30]  Weidong Yang,et al.  Shape control of CdSe nanocrystals , 2000, Nature.

[31]  P. Devarajan,et al.  Engineered nanocarriers of doxorubicin: a current update. , 2008, Critical reviews in therapeutic drug carrier systems.

[32]  G. Rasi,et al.  Induction of apoptosis in neoplastic cells by anthracycline antitumor drugs: nuclear and cytoplasmic triggering? , 1999, Anticancer research.

[33]  Younan Xia,et al.  Transformation of Silver Nanospheres into Nanobelts and Triangular Nanoplates through a Thermal Process , 2003 .

[34]  C. Mirkin,et al.  Photoinduced Conversion of Silver Nanospheres to Nanoprisms , 2001, Science.

[35]  J. Hupp,et al.  Synthesis of silver nanodisks using polystyrene mesospheres as templates. , 2002, Journal of the American Chemical Society.

[36]  Stephen Hanessian,et al.  Synthesis of chemically functionalized superparamagnetic nanoparticles as delivery vectors for chemotherapeutic drugs. , 2008, Bioorganic & medicinal chemistry.

[37]  S. Nie,et al.  Therapeutic Nanoparticles for Drug Delivery in Cancer Types of Nanoparticles Used as Drug Delivery Systems , 2022 .

[38]  El Sayed SOME INTERESTING PROPERTIES OF METALS CONFINED IN TIME AND NANOMETER SPACE OF DIFFERENT SHAPES , 2001 .

[39]  Baoan Chen,et al.  In vitro cellular uptake and cytotoxic effect of functionalized nickel nanoparticles on leukemia cancer cells. , 2008, Journal of nanoscience and nanotechnology.

[40]  D. Fernig,et al.  Determination of size and concentration of gold nanoparticles from UV-vis spectra. , 2007, Analytical chemistry.

[41]  Balaprasad Ankamwar,et al.  Biological synthesis of triangular gold nanoprisms , 2004, Nature materials.

[42]  M. Sarikaya,et al.  A genetic analysis of crystal growth. , 2000, Journal of molecular biology.

[43]  M. Steigerwald,et al.  Biosynthesis of cadmium sulphide quantum semiconductor crystallites , 1989, Nature.

[44]  Nicholas A. Kotov,et al.  Layer-by-Layer Assembled Mixed Spherical and Planar Gold Nanoparticles: Control of Interparticle Interactions , 2002 .

[45]  M. Pileni,et al.  Large triangular single crystals formed by mild annealing of self-organized silver nanocrystals. , 2007, Nature materials.

[46]  Carsten Sönnichsen,et al.  Separation of nanoparticles by gel electrophoresis according to size and shape. , 2007, Nano letters.