Surface chemistry and aspect ratio mediated cellular uptake of Au nanorods.

Gold nanorods (Au NRs) have been recognized as promising materials for biomedical applications, like sensing, imaging, gene and drug delivery and therapy, but their toxicological issues are still controversial, especially for the Au NRs synthesized with seed-mediated method. In this study, we investigated the influence of aspect ratio and surface coating on their toxicity and cellular uptake. The cellular uptake is highly dependent on the aspect ratio and surface coating. However, the surface chemistry has the dominant roles since PDDAC-coated Au NRs exhibit a much greater ability to be internalized by the cells. The present data demonstrated shape-independent but coating-dependent cytotoxicity. Both the CTAB molecules left in the suspended solution and on the surface of Au NRs were identified as the actual cause of cytotoxicity. CTAB can enter cells with or without Au NRs, damage mitochondria, and then induce apoptosis. The effects of surface coating upon toxicity and cellular uptake were also examined using Au NRs with different coatings. When Au NRs were added into the medium, the proteins were quickly adsorbed onto the Au NRs that made the surface negatively charged. The surface charge may not directly affect the cellular uptake. We further demonstrated that the amount of serum proteins, especially for BSA, adsorbed on the Au NRs had a positive correlation with the capacity of Au NRs to enter cells. In addition, we have successfully revealed that the cationic PDDAC-coated Au NRs with an aspect ratio of 4 possess an ideal combination of both negligible toxicity and high cellular uptake efficiency, showing a great promise as photothermal therapeutic agents.

[1]  Xiaohua Huang,et al.  Gold Nanorods: From Synthesis and Properties to Biological and Biomedical Applications , 2009, Advanced materials.

[2]  P. Jain,et al.  Au nanoparticles target cancer , 2007 .

[3]  Glenn P. Goodrich,et al.  Photothermal Efficiencies of Nanoshells and Nanorods for Clinical Therapeutic Applications , 2009 .

[4]  Y. Kaneda,et al.  Normalizing mitochondrial superoxide production blocks three pathways of hyperglycaemic damage , 2000, Nature.

[5]  F. Buttgereit,et al.  A hierarchy of ATP-consuming processes in mammalian cells. , 1995, The Biochemical journal.

[6]  Wei Li,et al.  Fullerene nanoparticles selectively enter oxidation-damaged cerebral microvessel endothelial cells and inhibit JNK-related apoptosis. , 2009, ACS nano.

[7]  Alaaldin M. Alkilany,et al.  Gold nanoparticles in biology: beyond toxicity to cellular imaging. , 2008, Accounts of chemical research.

[8]  Curtis D. Klaassen,et al.  Casarett and Doull's Toxicology. The Basic Science of Poisons , 1981 .

[9]  Ji-Xin Cheng,et al.  Gold Nanorods Mediate Tumor Cell Death by Compromising Membrane Integrity , 2007, Advanced materials.

[10]  Hamidreza Ghandehari,et al.  Cellular uptake and toxicity of gold nanoparticles in prostate cancer cells: a comparative study of rods and spheres , 2009, Journal of applied toxicology : JAT.

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

[12]  Marcus Textor,et al.  Bovine serum albumin adsorption onto colloidal Al2O3 particles: a new model based on zeta potential and UV-vis measurements. , 2004, Langmuir : the ACS journal of surfaces and colloids.

[13]  Srirang Manohar,et al.  In vitro toxicity studies of polymer-coated gold nanorods , 2010, Nanotechnology.

[14]  Erik C. Dreaden,et al.  Gold nanorod assisted near-infrared plasmonic photothermal therapy (PPTT) of squamous cell carcinoma in mice. , 2008, Cancer letters.

[15]  Ji-Xin Cheng,et al.  Gold nanorod-mediated photothermolysis induces apoptosis of macrophages via damage of mitochondria. , 2009, Nanomedicine.

[16]  Kostas Kostarelos,et al.  The emergence of nanomedicine: a field in the making. , 2006, Nanomedicine.

[17]  Travis L. Jennings,et al.  Enhancing the Toxicity of Cancer Chemotherapeutics with Gold Nanorod Hyperthermia , 2008 .

[18]  Ji-Xin Cheng,et al.  Controlling the cellular uptake of gold nanorods. , 2007, Langmuir : the ACS journal of surfaces and colloids.

[19]  Ying Liu,et al.  Characterization of gold nanorods in vivo by integrated analytical techniques: their uptake, retention, and chemical forms , 2010, Analytical and bioanalytical chemistry.

[20]  V. Darley-Usmar,et al.  The powerhouse takes control of the cell; the role of mitochondria in signal transduction. , 2004, Free radical biology & medicine.

[21]  D. Green,et al.  Mitochondrial outer membrane permeabilization during apoptosis: the innocent bystander scenario , 2006, Cell Death and Differentiation.

[22]  Vincent M Rotello,et al.  Toxicity of gold nanoparticles functionalized with cationic and anionic side chains. , 2004, Bioconjugate chemistry.

[23]  Catherine J Murphy,et al.  Seeded high yield synthesis of short Au nanorods in aqueous solution. , 2004, Langmuir : the ACS journal of surfaces and colloids.

[24]  Weiya Zhou,et al.  Well-controlled synthesis of Au@Pt nanostructures by gold-nanorod-seeded growth. , 2008, Chemistry.

[25]  Catherine J. Murphy,et al.  Seed‐Mediated Growth Approach for Shape‐Controlled Synthesis of Spheroidal and Rod‐like Gold Nanoparticles Using a Surfactant Template , 2001 .

[26]  Xiaohua Huang,et al.  Cancer cell imaging and photothermal therapy in the near-infrared region by using gold nanorods. , 2006, Journal of the American Chemical Society.

[27]  M. Hengartner The biochemistry of apoptosis , 2000, Nature.

[28]  Paul C. Wang,et al.  The scavenging of reactive oxygen species and the potential for cell protection by functionalized fullerene materials. , 2009, Biomaterials.

[29]  Sandra L. Schmid,et al.  Regulated portals of entry into the cell , 2003, Nature.

[30]  Lorenzo Galluzzi,et al.  Mitochondrial membrane permeabilization in cell death. , 2007, Physiological reviews.

[31]  T. Xia,et al.  Understanding biophysicochemical interactions at the nano-bio interface. , 2009, Nature materials.

[32]  M. El-Sayed,et al.  Simulation of the Optical Absorption Spectra of Gold Nanorods as a Function of Their Aspect Ratio and the Effect of the Medium Dielectric Constant , 1999 .

[33]  Arezou A Ghazani,et al.  Assessing the effect of surface chemistry on gold nanorod uptake, toxicity, and gene expression in mammalian cells. , 2008, Small.

[34]  Arezou A Ghazani,et al.  Determining the size and shape dependence of gold nanoparticle uptake into mammalian cells. , 2006, Nano letters.

[35]  C. Murphy,et al.  Gold nanoparticles are taken up by human cells but do not cause acute cytotoxicity. , 2005, Small.

[36]  Feldmann,et al.  Drastic reduction of plasmon damping in gold nanorods. , 2002, Physical review letters.

[37]  John A. Pickrell,et al.  Casarett and Doull's toxicology: The basic science of poisons , 1996 .

[38]  Frank Caruso,et al.  Nanoengineering of particle surfaces. , 2001 .

[39]  H. McBride,et al.  Mitochondria: More Than Just a Powerhouse , 2006, Current Biology.

[40]  Hong Ding,et al.  Gold Nanorods Coated with Multilayer Polyelectrolyte as Contrast Agents for Multimodal Imaging , 2007 .

[41]  Weihong Tan,et al.  Selective photothermal therapy for mixed cancer cells using aptamer-conjugated nanorods. , 2008, Langmuir : the ACS journal of surfaces and colloids.

[42]  P. Jain,et al.  Calculated absorption and scattering properties of gold nanoparticles of different size, shape, and composition: applications in biological imaging and biomedicine. , 2006, The journal of physical chemistry. B.

[43]  Younan Xia,et al.  Gold and silver nanoparticles: a class of chromophores with colors tunable in the range from 400 to 750 nm. , 2003, The Analyst.

[44]  Timothy J Shaw,et al.  Cellular uptake and cytotoxicity of gold nanorods: molecular origin of cytotoxicity and surface effects. , 2009, Small.

[45]  M. Dobrovolskaia,et al.  Immunological properties of engineered nanomaterials , 2007, Nature Nanotechnology.

[46]  C. Murphy,et al.  Polyelectrolyte-Coated Gold Nanorods: Synthesis, Characterization and Immobilization , 2005 .

[47]  Younan Xia,et al.  Measuring the Optical Absorption Cross-sections of Au-Ag Nanocages and Au Nanorods by Photoacoustic Imaging. , 2009, The journal of physical chemistry. C, Nanomaterials and interfaces.

[48]  Younan Xia,et al.  Dark-field microscopy studies of single metal nanoparticles: understanding the factors that influence the linewidth of the localized surface plasmon resonance. , 2008, Journal of materials chemistry.

[49]  T. Xia,et al.  Toxic Potential of Materials at the Nanolevel , 2006, Science.

[50]  Mostafa A. El-Sayed,et al.  Preparation and Growth Mechanism of Gold Nanorods (NRs) Using Seed-Mediated Growth Method , 2003 .

[51]  M. Kula,et al.  Biomass/adsorbent electrostatic interactions in expanded bed adsorption: a zeta potential study. , 2003, Biotechnology and bioengineering.

[52]  C. Murphy,et al.  Quantitation of metal content in the silver-assisted growth of gold nanorods. , 2006, The journal of physical chemistry. B.

[53]  Y. Liu,et al.  The effect of Gd@C82(OH)22 nanoparticles on the release of Th1/Th2 cytokines and induction of TNF-alpha mediated cellular immunity. , 2009, Biomaterials.

[54]  D. Tsai,et al.  Biosensing, Cytotoxicity, and Cellular Uptake Studies of Surface-Modified Gold Nanorods , 2009 .