Cationic surface modification of gold nanoparticles for enhanced cellular uptake and X-ray radiation therapy.

A challenge of X-ray radiation therapy is that high dose X-ray can damage normal cells and cause side effects. This paper describes a new nanoparticle-based method to reduce X-ray dose in radiation therapy by internalization of gold nanoparticles that are modified with cationic molecules into cancer cells. A cationic thiol molecule is synthesized and used to modify gold nanoparticles in a one-step reaction. The modified nanoparticles can penetrate cell membranes at high yield. By bring radio-sensitizing gold nanoparticles closer to nuclei where DNA is stored, the total X-ray dose needed to kill cancer cells has been reduced. The simulation of X-ray-gold nanoparticle interaction also indicates that Auger electrons contribute more than photoelectrons.

[1]  Mainul Hossain,et al.  Nanoparticle location and material dependent dose enhancement in X-ray radiation therapy. , 2012, The journal of physical chemistry. C, Nanomaterials and interfaces.

[2]  M. Dizdaroglu,et al.  Free radical-induced damage to DNA: mechanisms and measurement. , 2002, Free radical biology & medicine.

[3]  Valery V Tuchin,et al.  Circulation and distribution of gold nanoparticles and induced alterations of tissue morphology at intravenous particle delivery , 2009, Journal of biophotonics.

[4]  R. Barth,et al.  Boron neutron capture therapy of cancer. , 1990, Cancer research.

[5]  Shuk Han Cheng,et al.  Nuclear penetration of surface functionalized gold nanoparticles. , 2009, Toxicology and applied pharmacology.

[6]  S. Franzen,et al.  Multifunctional gold nanoparticle-peptide complexes for nuclear targeting. , 2003, Journal of the American Chemical Society.

[7]  J. V. van Lier,et al.  Metal complexes as photo- and radiosensitizers. , 1999, Chemical reviews.

[8]  H. Gümüş,et al.  Electron inelastic mean free path formula and CSDA-range calculation in biological compounds for low and intermediate energies. , 2006, Applied radiation and isotopes : including data, instrumentation and methods for use in agriculture, industry and medicine.

[9]  Tae Gwan Park,et al.  Target-specific cellular uptake of PLGA nanoparticles coated with poly(L-lysine)-poly(ethylene glycol)-folate conjugate. , 2005, Langmuir : the ACS journal of surfaces and colloids.

[10]  B. Meunier,et al.  Carbon—Hydrogen Bonds of DNA Sugar Units as Targets for Chemical Nucleases and Drugs , 1995 .

[11]  T. Tullius,et al.  Oxidative Strand Scission of Nucleic Acids: Routes Initiated by Hydrogen Abstraction from the Sugar Moiety. , 1998, Chemical reviews.

[12]  D. Schulte‐Frohlinde,et al.  Radiolysis of DNA in aqueous solution in the presence of a scavenger: A kinetic model based on a nonhomogeneous reaction of OH radicals with DNA molecules of spherical or cylindrical shape , 1989, Radiation and environmental biophysics.

[13]  X. Le,et al.  Inducible repair of thymine glycol detected by an ultrasensitive assay for DNA damage. , 1998, Science.

[14]  Y. Averkov,et al.  Nonlinear oscillations of a semiconductor plasma with a nonrelativistic electron beam , 2002 .

[15]  J. Fowler,et al.  Radiosensitization of Chinese hamster cells by oxygen and misonidazole at low X-ray doses. , 1986, International journal of radiation biology and related studies in physics, chemistry, and medicine.

[16]  E. Zubarev,et al.  Quantitative replacement of cetyl trimethylammonium bromide by cationic thiol ligands on the surface of gold nanorods and their extremely large uptake by cancer cells. , 2012, Angewandte Chemie.

[17]  Mansoor Amiji,et al.  Long-Circulating Poly(Ethylene Glycol)-Modified Gelatin Nanoparticles for Intracellular Delivery , 2002, Pharmaceutical Research.

[18]  David K. Wood,et al.  Single cell trapping and DNA damage analysis using microwell arrays , 2010, Proceedings of the National Academy of Sciences.

[19]  G. Hanks,et al.  Radiation inactivation of human prostate cancer cells: the role of apoptosis. , 1996, Radiation research.

[20]  R. Lease,et al.  Hydroxyl radical footprinting in vivo: mapping macromolecular structures with synchrotron radiation , 2006, Nucleic acids research.

[21]  B. Lehnert,et al.  Radiation-induced effects in unirradiated cells: a review and implications in cancer. , 2002, International journal of oncology.

[22]  S. Hosseinimehr Trends in the development of radioprotective agents. , 2007, Drug discovery today.

[23]  S. Wallace Serial Review: Oxidative DNA Damage and Repair Guest Editor: Miral Dizdaroglu BIOLOGICAL CONSEQUENCES OF FREE RADICAL-DAMAGED DNA BASES , 2002 .

[24]  P. Wardman,et al.  Chemical radiosensitizers for use in radiotherapy. , 2007, Clinical oncology (Royal College of Radiologists (Great Britain)).

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

[26]  B. Godley,et al.  Blue Light Induces Mitochondrial DNA Damage and Free Radical Production in Epithelial Cells* , 2005, Journal of Biological Chemistry.

[27]  Francesco Stellacci,et al.  Surface-structure-regulated cell-membrane penetration by monolayer-protected nanoparticles. , 2008, Nature materials.

[28]  Petra Krystek,et al.  Particle size-dependent organ distribution of gold nanoparticles after intravenous administration. , 2008, Biomaterials.

[29]  T. Tullius,et al.  DNA strand breaking by the hydroxyl radical is governed by the accessible surface areas of the hydrogen atoms of the DNA backbone. , 1998, Proceedings of the National Academy of Sciences of the United States of America.

[30]  C. Chatgilialoglu,et al.  Free radicals associated with DNA damage , 2001, Experimental Gerontology.

[31]  C. Borek Antioxidants and radiation therapy. , 2004, The Journal of nutrition.

[32]  H. Kohler,et al.  Chemical engineering of cell penetrating antibodies. , 2001, Journal of immunological methods.

[33]  Ronald C. Chen,et al.  Folate-targeted polymeric nanoparticle formulation of docetaxel is an effective molecularly targeted radiosensitizer with efficacy dependent on the timing of radiotherapy. , 2011, ACS nano.

[34]  Francesco Stellacci,et al.  Effect of surface properties on nanoparticle-cell interactions. , 2010, Small.

[35]  Petras Juzenas,et al.  Quantum dots and nanoparticles for photodynamic and radiation therapies of cancer. , 2008, Advanced drug delivery reviews.