CuS Nanodots with Ultrahigh Efficient Renal Clearance for Positron Emission Tomography Imaging and Image-Guided Photothermal Therapy.

Translation of nanoparticles (NPs) into clinical practice has been limited by toxic effects induced by nonspecific accumulation of NPs in healthy organs after systemic administration. The ideal NPs should accumulate in the target site, carry out their function, and then ultimately be eliminated from the body. Here, we show a single-compartment, multifunctional ultrasmall copper sulfide nanodot (CuS ND) that is rapidly cleared from the body. These CuS NDs have a hydrodynamic diameter of <6 nm, can efficiently absorb near-infrared light for photothermal ablation therapy, and stably incorporate the copper-64 radioisotope for noninvasive positron emission tomography (PET). Importantly, ∼95% of CuS NDs are excreted intact through the renal-urinary system within 24 h with minimal retention in the liver and the spleen. The ultrasmall CuS NDs accumulate in 4T1 tumors in Balb/c mice, as monitored by PET imaging, and mediate tumor ablation when combined with near-infrared light irradiation. As a first example of PET-visible, renal-clearable inorganic nanomaterials with peak absorption in the near-infrared region, CuS NDs represent a robust platform for cancer imaging and therapy.

[1]  R. Stafford,et al.  Nanoshell-mediated near-infrared thermal therapy of tumors under magnetic resonance guidance , 2003, Proceedings of the National Academy of Sciences of the United States of America.

[2]  H. Choi,et al.  In vivo near-infrared mediated tumor destruction by photothermal effect of carbon nanotubes. , 2009, ACS Nano.

[3]  Kai Yang,et al.  Graphene in mice: ultrahigh in vivo tumor uptake and efficient photothermal therapy. , 2010, Nano letters.

[4]  H. Dai,et al.  In vivo biodistribution and highly efficient tumour targeting of carbon nanotubes in mice. , 2020, Nature nanotechnology.

[5]  Jesse V Jokerst,et al.  Nanoparticle PEGylation for imaging and therapy. , 2011, Nanomedicine.

[6]  Jie Zheng,et al.  Passive tumor targeting of renal-clearable luminescent gold nanoparticles: long tumor retention and fast normal tissue clearance. , 2013, Journal of the American Chemical Society.

[7]  Hui Zhang,et al.  Immuno gold nanocages with tailored optical properties for targeted photothermal destruction of cancer cells. , 2007, Nano letters.

[8]  Younan Xia,et al.  Gold nanocages as photothermal transducers for cancer treatment. , 2010, Small.

[9]  Chen-Sheng Yeh,et al.  Near-infrared light-responsive nanomaterials in cancer therapeutics. , 2014, Chemical Society reviews.

[10]  Jie Zheng,et al.  Luminescent gold nanoparticles with efficient renal clearance. , 2011, Angewandte Chemie.

[11]  Simon M. Ametamey,et al.  Molecular Imaging with PET , 2008 .

[12]  Sanjiv S Gambhir,et al.  Nanooncology: The future of cancer diagnosis and therapy , 2013, CA: a cancer journal for clinicians.

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

[14]  Mark E. Davis,et al.  Nanoparticle therapeutics: an emerging treatment modality for cancer , 2008, Nature Reviews Drug Discovery.

[15]  H. Dai,et al.  Ultrasmall reduced graphene oxide with high near-infrared absorbance for photothermal therapy. , 2011, Journal of the American Chemical Society.

[16]  Hak Soo Choi,et al.  Design considerations for tumour-targeted nanoparticles. , 2010, Nature nanotechnology.

[17]  D. Scheinberg,et al.  Conscripts of the infinite armada: systemic cancer therapy using nanomaterials , 2010, Nature Reviews Clinical Oncology.

[18]  Meifang Zhu,et al.  Hydrophilic Flower‐Like CuS Superstructures as an Efficient 980 nm Laser‐Driven Photothermal Agent for Ablation of Cancer Cells , 2011, Advanced materials.

[19]  L. Spiccia,et al.  Zwitterionic Coatings: Zwitterionic‐Coated “Stealth” Nanoparticles for Biomedical Applications: Recent Advances in Countering Biomolecular Corona Formation and Uptake by the Mononuclear Phagocyte System (Small 13/2014) , 2014 .

[20]  Hak Soo Choi,et al.  Tissue- and organ-selective biodistribution of NIR fluorescent quantum dots. , 2009, Nano letters.

[21]  Wenxiu Zhao,et al.  Engineered iron-oxide-based nanoparticles as enhanced T1 contrast agents for efficient tumor imaging. , 2013, ACS nano.

[22]  Jie Zheng,et al.  PEGylation and zwitterionization: pros and cons in the renal clearance and tumor targeting of near-IR-emitting gold nanoparticles. , 2013, Angewandte Chemie.

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

[24]  Chen Zhou,et al.  Renal clearable inorganic nanoparticles: A new frontier of bionanotechnology , 2013 .

[25]  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.

[26]  Chun Xing Li,et al.  Pharmacokinetics, clearance, and biosafety of polyethylene glycol-coated hollow gold nanospheres , 2014, Particle and Fibre Toxicology.

[27]  D. Dupuy,et al.  Thermal ablation of tumours: biological mechanisms and advances in therapy , 2014, Nature Reviews Cancer.

[28]  Chao He,et al.  Insights into the surface property and blood compatibility of polyethersulfone/polyvinylpyrrolidone composite membranes: toward high‐performance hemodialyzer , 2014 .

[29]  C. Xiong,et al.  Effective photothermal chemotherapy using doxorubicin-loaded gold nanospheres that target EphB4 receptors in tumors. , 2012, Cancer research.

[30]  Chun Li,et al.  A targeted approach to cancer imaging and therapy. , 2014, Nature materials.

[31]  R. Service.  Nanotechnology Takes Aim at Cancer , 2005, Science.

[32]  K. Sakai,et al.  Nanotechnological Characterization of Human Serum Albumin Adsorption on Wet Synthetic Polymer Dialysis Membrane Surfaces , 2009, ASAIO journal.

[33]  Wei Lu,et al.  Hollow copper sulfide nanoparticle-mediated transdermal drug delivery. , 2012, Small.

[34]  Andrew S Torres,et al.  Preclinical assessment of a zwitterionic tantalum oxide nanoparticle X-ray contrast agent. , 2012, ACS nano.

[35]  Austin D. Swafford,et al.  Thermal ablation of tumor cells with antibody-functionalized single-walled carbon nanotubes , 2008, Proceedings of the National Academy of Sciences.

[36]  Liang Cheng,et al.  Functional nanomaterials for phototherapies of cancer. , 2014, Chemical reviews.

[37]  M. Melancon,et al.  Cancer theranostics with near-infrared light-activatable multimodal nanoparticles. , 2011, Accounts of chemical research.

[38]  Hak Soo Choi,et al.  Targeted zwitterionic near-infrared fluorophores for improved optical imaging , 2013, Nature Biotechnology.

[39]  Manuela Semmler-Behnke,et al.  Biodistribution of 1.4- and 18-nm gold particles in rats. , 2008, Small.

[40]  Xiaohua Huang,et al.  Applications of gold nanorods for cancer imaging and photothermal therapy. , 2010, Methods in molecular biology.

[41]  G. Ku,et al.  Theranostic probe for simultaneous in vivo photoacoustic imaging and confined photothermolysis by pulsed laser at 1064 nm in 4T1 breast cancer model. , 2014, Nanoscale.

[42]  Robert Sinclair,et al.  Particle size, surface coating, and PEGylation influence the biodistribution of quantum dots in living mice. , 2008, Small.

[43]  Dong Liang,et al.  A chelator-free multifunctional [64Cu]CuS nanoparticle platform for simultaneous micro-PET/CT imaging and photothermal ablation therapy. , 2010, Journal of the American Chemical Society.

[44]  Xin Wang,et al.  Biodistribution of Pristine Single-Walled Carbon Nanotubes In Vivo† , 2007 .

[45]  Matthew G. Panthani,et al.  Copper selenide nanocrystals for photothermal therapy. , 2011, Nano letters.

[46]  Hong Chen,et al.  Protein adsorption on poly(N-vinylpyrrolidone)-modified silicon surfaces prepared by surface-initiated atom transfer radical polymerization. , 2009, Langmuir : the ACS journal of surfaces and colloids.

[47]  R. Stafford,et al.  Targeted multifunctional gold-based nanoshells for magnetic resonance-guided laser ablation of head and neck cancer. , 2011, Biomaterials.

[48]  Chun Xing Li,et al.  An ultra pH-sensitive and aptamer-equipped nanoscale drug-delivery system for selective killing of tumor cells. , 2013, Small.