The influence of tumor-induced immune dysfunction on the immune cell distribution of gold nanoparticles in vivo.

Gold nanoparticles (AuNPs) have been extensively explored as a drug carrier and have been widely used to provide advanced biomedical research tools in diagnostic imaging and therapy for cancer. Although the mononuclear phagocyte system and immune system are known to play the main roles in the clearance of AuNPs during the circulation, the particle distribution within the immune cells under the condition of immune dysfunction caused by tumor growth has not been thoroughly studied. Here, the cellular distribution of Cy5 labeled AuNPs with diameters of 5, 30 and 50 nm is characterized within the immune populations of the blood, spleen and bone marrow from tumor free and tumor bearing mice using flow cytometry. Tumor-associated immune dysfunction was observed in all immune organs and cell lineages, and it changed with tumor growth. Furthermore, the particle cellular distribution significantly changed in the tumor bearing mice compared with the tumor free mice. Finally, the particle distribution in the immune cells was also different at different stages of the tumor. Overall, these results can help inform and influence future AuNP design criteria including the future applications for nanoparticle-mediated cancer therapy.

[1]  T. Weil,et al.  NIR-emitting and photo-thermal active nanogold as mitochondria-specific probes. , 2017, Biomaterials science.

[2]  C. Kirkpatrick,et al.  Gold nanoparticle interactions with endothelial cells cultured under physiological conditions. , 2017, Biomaterials science.

[3]  Timothy Z. Chang,et al.  Effects of ovalbumin protein nanoparticle vaccine size and coating on dendritic cell processing. , 2017, Biomaterials science.

[4]  F J Beekman,et al.  In vivo biodistribution of stable spherical and filamentous micelles probed by high-sensitivity SPECT. , 2016, Biomaterials science.

[5]  Yuanxin Chen,et al.  Surface modification of nanoparticles enables selective evasion of phagocytic clearance by distinct macrophage phenotypes , 2016, Scientific Reports.

[6]  Xianzhu Yang,et al.  A block copolymer of zwitterionic polyphosphoester and polylactic acid for drug delivery. , 2015, Biomaterials science.

[7]  Dong Choon Hyun,et al.  Engineered nanoparticles for drug delivery in cancer therapy. , 2014, Angewandte Chemie.

[8]  R. Mach,et al.  Using SV119‐Gold Nanocage Conjugates to Eradicate Cancer Stem Cells Through a Combination of Photothermal and Chemo Therapies , 2014, Advanced healthcare materials.

[9]  A. Poggi,et al.  Mechanisms of tumor escape from immune system: role of mesenchymal stromal cells. , 2014, Immunology letters.

[10]  R. Drezek,et al.  In vivo immune cell distribution of gold nanoparticles in naïve and tumor bearing mice. , 2014, Small.

[11]  H. Schreiber,et al.  Innate and adaptive immune cells in the tumor microenvironment , 2013, Nature Immunology.

[12]  Michael J Welch,et al.  Nucleic Acid-directed Self-assembly of Multifunctional Gold Nanoparticle Imaging Agents. , 2013, Biomaterials science.

[13]  Umesh Kumar,et al.  Cellular Binding of Anionic Nanoparticles is Inhibited by Serum Proteins Independent of Nanoparticle Composition. , 2013, Biomaterials science.

[14]  R. Drezek,et al.  Elimination of Metastatic Melanoma Using Gold Nanoshell-Enabled Photothermal Therapy and Adoptive T Cell Transfer , 2013, PloS one.

[15]  James E Bear,et al.  Nanoparticle clearance is governed by Th1/Th2 immunity and strain background. , 2013, The Journal of clinical investigation.

[16]  Tadaki Suzuki,et al.  Gold nanoparticles as a vaccine platform: influence of size and shape on immunological responses in vitro and in vivo. , 2013, ACS nano.

[17]  Younan Xia,et al.  Seed-mediated synthesis of single-crystal gold nanospheres with controlled diameters in the range 5-30 nm and their self-assembly upon dilution. , 2013, Chemistry, an Asian journal.

[18]  Pascal Richette,et al.  Antibodies against polyethylene glycol in healthy subjects and in patients treated with PEG-conjugated agents , 2012, Expert opinion on drug delivery.

[19]  Chun Xing Li,et al.  Photothermal-chemotherapy with doxorubicin-loaded hollow gold nanospheres: A platform for near-infrared light-trigged drug release. , 2012, Journal of controlled release : official journal of the Controlled Release Society.

[20]  Vincent Castranova,et al.  Toxicology of Nanomaterials Used in Nanomedicine , 2011, Journal of toxicology and environmental health. Part B, Critical reviews.

[21]  Rebekah Drezek,et al.  In vivo biodistribution of nanoparticles. , 2011, Nanomedicine.

[22]  Jun Wang,et al.  Doxorubicin-tethered responsive gold nanoparticles facilitate intracellular drug delivery for overcoming multidrug resistance in cancer cells. , 2011, ACS nano.

[23]  Lev Dykman,et al.  Biodistribution and toxicity of engineered gold nanoparticles: a review of in vitro and in vivo studies. , 2011, Chemical Society reviews.

[24]  L. Yang.  TGFbeta, a potent regulator of tumor microenvironment and host immune response, implication for therapy. , 2010, Current molecular medicine.

[25]  Wei Lu,et al.  Tumor Site–Specific Silencing ofNF-κB p65by Targeted Hollow Gold Nanosphere–Mediated Photothermal Transfection , 2010, Cancer Research.

[26]  M. Karin,et al.  Immunity, Inflammation, and Cancer , 2010, Cell.

[27]  Warren C W Chan,et al.  Mediating tumor targeting efficiency of nanoparticles through design. , 2009, Nano letters.

[28]  Dong Liang,et al.  Influence of anchoring ligands and particle size on the colloidal stability and in vivo biodistribution of polyethylene glycol-coated gold nanoparticles in tumor-xenografted mice. , 2009, Biomaterials.

[29]  P. Choyke,et al.  Clearance properties of nano-sized particles and molecules as imaging agents: considerations and caveats. , 2008, Nanomedicine.

[30]  M. Bawendi,et al.  Renal clearance of quantum dots , 2007, Nature Biotechnology.

[31]  James A J Fitzpatrick,et al.  Sentinel lymph node imaging using quantum dots in mouse tumor models. , 2007, Bioconjugate chemistry.

[32]  M. El-Sayed,et al.  Chemistry and properties of nanocrystals of different shapes. , 2005, Chemical reviews.

[33]  S M Moghimi,et al.  Long-circulating and target-specific nanoparticles: theory to practice. , 2001, Pharmacological reviews.

[34]  V. Kolb-Bachofen,et al.  Coating particles with a block co-polymer (poloxamine-908) suppresses opsonization but permits the activity of dysopsonins in the serum. , 1993, Biochimica et biophysica acta.

[35]  Yang Liu,et al.  Cancer stem cell therapy using doxorubicin conjugated to gold nanoparticles via hydrazone bonds. , 2014, Biomaterials.