Biodistribution of TNF-alpha-coated gold nanoparticles in an in vivo model system.

AIM In this study, we describe the biodistribution of CYT-6091, a colloidal gold (Au)-based nanomedicine that targets the delivery of TNF-alpha to solid tumors. MATERIALS & METHODS A single intravenous injection of CYT-6091 coated with 5 microg TNF-alpha was given to human prostate tumor-bearing or naive (without tumor) nude mice. Tissues were harvested and analyzed at specific time points for Au nanoparticles by atomic emission spectroscopy and TNF-alpha by ELISA. RESULTS The two constituents of CYT-6091, TNF-alpha and Au, exhibited different behavior in blood, with TNF-alpha showing a faster decay than the Au nanoparticles. Between 0 and 4 h after injection, TNF-alpha showed a preferential accumulation in the tumor. Au was observed to accumulate preferentially in the liver between 4 and 12 h, and showed some clearance over time (4 months). CONCLUSION These data suggest that CYT-6091 delivers TNF-alpha preferentially to the tumor and that upon TNF-alpha degradation, the liver takes up Au, which is cleared slowly over time.

[1]  Parag Aggarwal,et al.  Preclinical studies to understand nanoparticle interaction with the immune system and its potential effects on nanoparticle biodistribution. , 2008, Molecular pharmaceutics.

[2]  H. Alexander,et al.  Direct evidence for rapid and selective induction of tumor neovascular permeability by tumor necrosis factor and a novel derivative, colloidal gold bound tumor necrosis factor , 2007, International journal of cancer.

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

[4]  J. Bischof,et al.  TNF-α–based accentuation in cryoinjury—dose, delivery, and response , 2007, Molecular Cancer Therapeutics.

[5]  M. Delano,et al.  Emerging implications of nanotechnology on cancer diagnostics and therapeutics , 2006, Cancer.

[6]  G. Harms,et al.  Zonal heterogeneity of rat hepatocytes in the in vivo uptake of 17 nm colloidal gold granules , 2004, Histochemistry.

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

[8]  Lawrence Tamarkin,et al.  Colloidal Gold: A Novel Nanoparticle Vector for Tumor Directed Drug Delivery , 2004, Drug delivery.

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

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

[11]  Shuming Nie,et al.  Emerging use of nanoparticles in diagnosis and treatment of breast cancer. , 2006, The Lancet. Oncology.

[12]  Parag Aggarwal,et al.  Interaction of colloidal gold nanoparticles with human blood: effects on particle size and analysis of plasma protein binding profiles. , 2009, Nanomedicine : nanotechnology, biology, and medicine.

[13]  Hillyer,et al.  Correlative Instrumental Neutron Activation Analysis, Light Microscopy, Transmission Electron Microscopy, and X-ray Microanalysis for Qualitative and Quantitative Detection of Colloidal Gold Spheres in Biological Specimens , 1998, Microscopy and Microanalysis.

[14]  E. Ebbini,et al.  Nanotherapeutics for enhancing thermal therapy of cancer , 2007, International journal of hyperthermia : the official journal of European Society for Hyperthermic Oncology, North American Hyperthermia Group.

[15]  M. Ferrari.  Cancer nanotechnology: opportunities and challenges , 2005, Nature Reviews Cancer.

[16]  Warren C W Chan,et al.  Elucidating the mechanism of cellular uptake and removal of protein-coated gold nanoparticles of different sizes and shapes. , 2007, Nano letters.

[17]  Takuro Niidome,et al.  PEG-modified gold nanorods with a stealth character for in vivo applications. , 2006, Journal of controlled release : official journal of the Controlled Release Society.

[18]  R. Havel,et al.  Hepatic metabolism of colloidal gold‐low‐density lipoprotein complexes in the rat: Evidence for bulk excretion of lysosomal contents into bile , 1989, Hepatology.

[19]  Kwon-Ha Yoon,et al.  Colloidal Gold Nanoparticles as a Blood-Pool Contrast Agent for X-ray Computed Tomography in Mice , 2007, Investigative radiology.