Fe3 O4 @Au@Cu2- x S Heterostructures Designed for Tri-Modal Therapy: Photo- Magnetic Hyperthermia and 64 Cu Radio-Insertion.

Here, the synthesis and proof of exploitation of three-material inorganic heterostructures made of iron oxide-gold-copper sulfide (Fe3 O4 @Au@Cu2- x S) are reported. Starting with Fe3 O4 -Au dumbbell heterostructure as seeds, a third Cu2- x S domain is selectively grown on the Au domain. The as-synthesized trimers are transferred to water by a two-step ligand exchange procedure exploiting thiol-polyethylene glycol to coordinate Au and Cu2- x S surfaces and polycatechol-polyethylene glycol to bind the Fe3 O4 surface. The saline stable trimers possess multi-functional properties: the Fe3 O4 domain, of appropriate size and crystallinity, guarantees optimal heating losses in magnetic hyperthermia (MHT) under magnetic field conditions of clinical use. These trimers have indeed record values of specific adsorption rate among the inorganic-heterostructures so far reported. The presence of Au and Cu2- x S domains ensures a large adsorption which falls in the first near-infrared (NIR) biological window and is here exploited, under laser excitation at 808 nm, to produce photo-thermal heat alone or in combination with MHT obtained from the Fe3 O4 domain. Finally, an intercalation protocol with radioactive 64 Cu ions is developed on the Cu2- x S domain, reaching high radiochemical yield and specific activity making the Fe3 O4 @Au@Cu2- x S trimers suitable as carriers for 64 Cu in internal radiotherapy (iRT) and traceable by positron emission tomography (PET).

[1]  B. Kooi,et al.  Radiation damage and defect dynamics in 2D WS2: a low-voltage scanning transmission electron microscopy study , 2021, 2D Materials.

[2]  V. Ezersky,et al.  Chemoselective Insertion of a CdS Rod between Au/Metal-Oxide Heterodimers , 2021 .

[3]  T. Pellegrino,et al.  Cation Exchange Protocols to Radiolabel Aqueous Stabilized ZnS, ZnSe, and CuFeS2 Nanocrystals with 64Cu for Dual Radio‐ and Photo‐Thermal Therapy , 2020, Advanced functional materials.

[4]  Sun-Hee Kim,et al.  Functionalised mesoporous silica nanoparticles with excellent cytotoxicity against various cancer cells for pH-responsive and controlled drug delivery , 2019 .

[5]  Peng Wang,et al.  Recent Advances in Small Copper Sulfide Nanoparticles for Molecular Imaging and Tumor Therapy. , 2019, Molecular pharmaceutics.

[6]  Wei R. Chen,et al.  Nanomaterial Applications in Photothermal Therapy for Cancer , 2019, Materials.

[7]  C. Wilhelm,et al.  Iron Oxide Nanoflowers @ CuS Hybrids for Cancer Tri-Therapy: Interplay of Photothermal Therapy, Magnetic Hyperthermia and Photodynamic Therapy , 2019, Theranostics.

[8]  F. Ludwig,et al.  Fe2+ Deficiencies, FeO Subdomains, and Structural Defects Favor Magnetic Hyperthermia Performance of Iron Oxide Nanocubes into Intracellular Environment. , 2018, Nano letters.

[9]  Aiguo Wu,et al.  A facile fabrication route for binary transition metal oxide-based Janus nanoparticles for cancer theranostic applications , 2018, Nano Research.

[10]  R. Ivkov,et al.  Magnetic hyperthermia therapy for the treatment of glioblastoma: a review of the therapy’s history, efficacy and application in humans , 2018, International journal of hyperthermia : the official journal of European Society for Hyperthermic Oncology, North American Hyperthermia Group.

[11]  Yongmin Chang,et al.  High in Vivo Stability of 64Cu-Labeled Cross-Bridged Chelators Is a Crucial Factor in Improved Tumor Imaging of RGD Peptide Conjugates. , 2018, Journal of medicinal chemistry.

[12]  Mingli Chen,et al.  SERS-Fluorescence Dual-Mode pH-Sensing Method Based on Janus Microparticles. , 2017, ACS applied materials & interfaces.

[13]  D. Zhao,et al.  Dumbbell-Shaped Bi-component Mesoporous Janus Solid Nanoparticles for Biphasic Interface Catalysis. , 2017, Angewandte Chemie.

[14]  J. Alonso,et al.  Boosted Hyperthermia Therapy by Combined AC Magnetic and Photothermal Exposures in Ag/Fe3O4 Nanoflowers. , 2016, ACS applied materials & interfaces.

[15]  A Escarpa,et al.  "Shoot and Sense" Janus Micromotors-Based Strategy for the Simultaneous Degradation and Detection of Persistent Organic Pollutants in Food and Biological Samples. , 2016, Analytical chemistry.

[16]  Annibale Versari,et al.  Post-Synthesis Incorporation of ⁶⁴Cu in CuS Nanocrystals to Radiolabel Photothermal Probes: A Feasible Approach for Clinics. , 2015, Journal of the American Chemical Society.

[17]  Chen-Sheng Yeh,et al.  Rattle‐Type Fe3O4@CuS Developed to Conduct Magnetically Guided Photoinduced Hyperthermia at First and Second NIR Biological Windows , 2015 .

[18]  H. Mattoussi,et al.  A multifunctional polymer combining the imidazole and zwitterion motifs as a biocompatible compact coating for quantum dots. , 2015, Journal of the American Chemical Society.

[19]  Samuel Sanchez,et al.  Enzyme-Powered Hollow Mesoporous Janus Nanomotors. , 2015, Nano letters (Print).

[20]  X. Qu,et al.  Using Plasmonic Copper Sulfide Nanocrystals as Smart Light-Driven Sterilants. , 2015, ACS nano.

[21]  L. Liz‐Marzán,et al.  A General Method for Solvent Exchange of Plasmonic Nanoparticles and Self-Assembly into SERS-Active Monolayers , 2015, Langmuir : the ACS journal of surfaces and colloids.

[22]  L. Lartigue,et al.  The One Year Fate of Iron Oxide Coated Gold Nanoparticles in Mice. , 2015, ACS nano.

[23]  Yibin Ying,et al.  Multifunctional Janus hematite-silica nanoparticles: mimicking peroxidase-like activity and sensitive colorimetric detection of glucose. , 2015, ACS applied materials & interfaces.

[24]  Mark A Griswold,et al.  Magnetic Particle Imaging Tracers: State-of-the-Art and Future Directions. , 2015, The journal of physical chemistry letters.

[25]  Su Chen,et al.  Janus Suprabead Displays Derived from the Modified Photonic Crystals toward Temperature Magnetism and Optics Multiple Responses. , 2015, ACS applied materials & interfaces.

[26]  Haijun Wu,et al.  Lattice-mismatch-induced twinning for seeded growth of anisotropic nanostructures. , 2015, ACS nano.

[27]  Longfei Tan,et al.  Plasmonic copper sulfide nanocrystals exhibiting near-infrared photothermal and photodynamic therapeutic effects. , 2015, ACS nano.

[28]  Wanwan Li,et al.  Gold nanoparticles for photoacoustic imaging. , 2015, Nanomedicine.

[29]  H. Zeng,et al.  General synthetic approach to heterostructured nanocrystals based on noble metals and I-VI, II-VI, and I-III-VI metal chalcogenides. , 2014, Langmuir : the ACS journal of surfaces and colloids.

[30]  Wei Lu,et al.  Combinatorial Photothermal and Immuno Cancer Therapy Using Chitosan-Coated Hollow Copper Sulfide Nanoparticles , 2014, ACS nano.

[31]  Haotong Wei,et al.  The effects of composition and surface chemistry on the toxicity of quantum dots. , 2013, Journal of materials chemistry. B.

[32]  Kohei Soga,et al.  Upconverting and NIR emitting rare earth based nanostructures for NIR-bioimaging. , 2013, Nanoscale.

[33]  C. Sangregorio,et al.  Copper sulfide nanocrystals with tunable composition by reduction of covellite nanocrystals with Cu+ ions. , 2013, Journal of the American Chemical Society.

[34]  L. Spiccia,et al.  Design, synthesis, characterisation and in vitro studies of hydrophilic, colloidally stable, 64Cu(II)-labelled, ultra-small iron oxide nanoparticles in a range of human cell lines , 2013 .

[35]  Jung Young Kim,et al.  New bifunctional chelator for 64Cu-immuno-positron emission tomography. , 2013, Bioconjugate chemistry.

[36]  Rujia Zou,et al.  Sub-10 nm Fe3O4@Cu(2-x)S core-shell nanoparticles for dual-modal imaging and photothermal therapy. , 2013, Journal of the American Chemical Society.

[37]  L. Lartigue,et al.  Biodegradation of iron oxide nanocubes: high-resolution in situ monitoring. , 2013, ACS nano.

[38]  Andrew Tsourkas,et al.  Selective Targeting of Brain Tumors with Gold Nanoparticle-Induced Radiosensitization , 2013, PloS one.

[39]  Gang Zheng,et al.  Intrinsically copper-64-labeled organic nanoparticles as radiotracers. , 2012, Angewandte Chemie.

[40]  Patrick Couvreur,et al.  Magnetic nanoparticles: design and characterization, toxicity and biocompatibility, pharmaceutical and biomedical applications. , 2012, Chemical reviews.

[41]  Karl T. Butterworth,et al.  Physical basis and biological mechanisms of gold nanoparticle radiosensitization. , 2012, Nanoscale.

[42]  Qian Huang,et al.  Copper sulfide nanoparticles as a new class of photoacoustic contrast agent for deep tissue imaging at 1064 nm. , 2012, ACS nano.

[43]  Liberato Manna,et al.  Water-soluble iron oxide nanocubes with high values of specific absorption rate for cancer cell hyperthermia treatment. , 2012, ACS nano.

[44]  Paresh Chandra Ray,et al.  Multifunctional plasmonic shell-magnetic core nanoparticles for targeted diagnostics, isolation, and photothermal destruction of tumor cells. , 2012, ACS nano.

[45]  Rujia Zou,et al.  Hydrophilic Cu9S5 nanocrystals: a photothermal agent with a 25.7% heat conversion efficiency for photothermal ablation of cancer cells in vivo. , 2011, ACS nano.

[46]  J. Ying,et al.  Seed-mediated synthesis, properties and application of γ-Fe2O3–CdSe magnetic quantum dots , 2011 .

[47]  F. Gendron,et al.  Long term in vivo biotransformation of iron oxide nanoparticles. , 2011, Biomaterials.

[48]  D. Russell,et al.  Targeted photodynamic therapy of breast cancer cells using antibody-phthalocyanine-gold nanoparticle conjugates , 2011, Photochemical & photobiological sciences : Official journal of the European Photochemistry Association and the European Society for Photobiology.

[49]  Fangming Zhan,et al.  Bifunctional nanoparticles with superparamagnetic and luminescence properties , 2011 .

[50]  Clare C. Byeon,et al.  Tumor regression in vivo by photothermal therapy based on gold-nanorod-loaded, functional nanocarriers. , 2011, ACS nano.

[51]  Wei Lu,et al.  Copper sulfide nanoparticles for photothermal ablation of tumor cells. , 2010, Nanomedicine.

[52]  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.

[53]  Shouheng Sun,et al.  A General Approach to Noble Metal−Metal Oxide Dumbbell Nanoparticles and Their Catalytic Application for CO Oxidation , 2010 .

[54]  Qizhi Zhang,et al.  Gold nanoparticles as a contrast agent for in vivo tumor imaging with photoacoustic tomography , 2009, Nanotechnology.

[55]  C. Anderson,et al.  Molecular imaging of cancer with copper-64 radiopharmaceuticals and positron emission tomography (PET). , 2009, Accounts of chemical research.

[56]  Taeghwan Hyeon,et al.  Inorganic Nanoparticles for MRI Contrast Agents , 2009 .

[57]  Unyoung Kim,et al.  Multitarget magnetic activated cell sorter , 2008, Proceedings of the National Academy of Sciences.

[58]  Jianping Xie,et al.  The synthesis of SERS-active gold nanoflower tags for in vivo applications. , 2008, ACS nano.

[59]  Raoul Kopelman,et al.  Targeted gold nanoparticles enable molecular CT imaging of cancer. , 2008, Nano letters.

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

[61]  Prashant K. Jain,et al.  Plasmonic photothermal therapy (PPTT) using gold nanoparticles , 2008, Lasers in Medical Science.

[62]  A. Balazs,et al.  Harnessing janus nanoparticles to create controllable pores in membranes. , 2008, ACS nano.

[63]  Xiaohua Huang,et al.  Noble metals on the nanoscale: optical and photothermal properties and some applications in imaging, sensing, biology, and medicine. , 2008, Accounts of chemical research.

[64]  Andreas Walther,et al.  Janus particles. , 2008, Soft matter.

[65]  Xiaohu Gao,et al.  Emerging application of quantum dots for drug delivery and therapy , 2008 .

[66]  Yadong Li,et al.  Bifunctional Au-Fe3O4 nanoparticles for protein separation. , 2007, ACS nano.

[67]  Arnab Roy,et al.  Characterization of enhanced antibacterial effects of novel silver nanoparticles , 2007, Nanotechnology.

[68]  Chun Li,et al.  Bifunctional Gold Nanoshells with a Superparamagnetic Iron Oxide-Silica Core Suitable for Both MR Imaging and Photothermal Therapy. , 2007, The journal of physical chemistry. C, Nanomaterials and interfaces.

[69]  J. Ying,et al.  Synthesis of silica-coated semiconductor and magnetic quantum dots and their use in the imaging of live cells. , 2007, Angewandte Chemie.

[70]  Dae Hong Jeong,et al.  Antimicrobial effects of silver nanoparticles. , 2007, Nanomedicine : nanotechnology, biology, and medicine.

[71]  A. Koong,et al.  Quantitative PET of EGFR expression in xenograft-bearing mice using 64Cu-labeled cetuximab, a chimeric anti-EGFR monoclonal antibody , 2007, European Journal of Nuclear Medicine and Molecular Imaging.

[72]  S. Song,et al.  Magnetic poly ε-caprolactone nanoparticles containing Fe3O4 and gemcitabine enhance anti-tumor effect in pancreatic cancer xenograft mouse model , 2007 .

[73]  Jinwoo Cheon,et al.  Biocompatible heterostructured nanoparticles for multimodal biological detection. , 2006, Journal of the American Chemical Society.

[74]  Toru Torii,et al.  Synthesis of Monodisperse Bicolored Janus Particles with Electrical Anisotropy Using a Microfluidic Co‐Flow System , 2006 .

[75]  Tymish Y. Ohulchanskyy,et al.  A general approach to binary and ternary hybrid nanocrystals. , 2006, Nano letters.

[76]  J F Hainfeld,et al.  Gold nanoparticles: a new X-ray contrast agent. , 2006, The British journal of radiology.

[77]  A Paul Alivisatos,et al.  Semiconductor nanocrystals for biological imaging , 2005, Current Opinion in Neurobiology.

[78]  Victor S-Y Lin,et al.  Stimuli-responsive controlled-release delivery system based on mesoporous silica nanorods capped with magnetic nanoparticles. , 2005, Angewandte Chemie.

[79]  Bernhard Gleich,et al.  Tomographic imaging using the nonlinear response of magnetic particles , 2005, Nature.

[80]  Shouheng Sun,et al.  Dumbbell-like bifunctional Au-Fe3O4 nanoparticles. , 2005, Nano letters.

[81]  Ryan Park,et al.  MicroPET imaging of breast cancer alphav-integrin expression with 64Cu-labeled dimeric RGD peptides. , 2004, Molecular imaging and biology : MIB : the official publication of the Academy of Molecular Imaging.

[82]  S. Nie,et al.  In vivo cancer targeting and imaging with semiconductor quantum dots , 2004, Nature Biotechnology.

[83]  Joachim O. Rädler,et al.  Hydrophobic Nanocrystals Coated with an Amphiphilic Polymer Shell: A General Route to Water Soluble Nanocrystals , 2004 .

[84]  Xiaobo Chen,et al.  Semiconductor quantum dots for photodynamic therapy. , 2003, Journal of the American Chemical Society.

[85]  D. A. Russell,et al.  Generation of Cytotoxic Singlet Oxygen via Phthalocyanine-Stabilized Gold Nanoparticles: A Potential Delivery Vehicle for Photodynamic Therapy , 2002 .

[86]  C Alexiou,et al.  Clinical applications of magnetic drug targeting. , 2001, The Journal of surgical research.

[87]  M. Welch,et al.  Radioimmunotherapy with a 64Cu-labeled monoclonal antibody: a comparison with 67Cu. , 1996, Proceedings of the National Academy of Sciences of the United States of America.

[88]  S. Wereley,et al.  soft matter , 2019, Science.

[89]  Shouheng Sun.  Au-Fe3O4 Dumbbell Nanoparticles as Dual-Functional Probes** , 2009 .