title: Biomineralization-Inspired Synthesis of Copper Sulfide-Ferritin Nanocages as Cancer Theranostics.
abstract: It is essential to control the size and morphology of nanoparticles strictly in nanomedicine. Protein cages offer significant potential for templated synthesis of inorganic nanoparticles. In this study, we successfully synthesized ultrasmall copper sulfide (CuS) nanoparticles inside the cavity of ferritin (Fn) nanocages by a biomimetic synthesis method. The uniform CuS-Fn nanocages (CuS-Fn NCs) showed strong near-infrared absorbance and high photothermal conversion efficiency. In quantitative ratiometric photoacoustic imaging (PAI), the CuS-Fn NCs exhibited superior photoacoustic tomography improvements for real-time in vivo PAI of entire tumors. With the incorporation of radionuclide (64)Cu, (64)CuS-Fn NCs also served as an excellent PET imaging agent with higher tumor accumulation compared to free copper. Following the guidance of PAI and PET, CuS-Fn NCs were applied in photothermal therapy to achieve superior cancer therapeutic efficiency with good biocompatibility both in vitro and in vivo. The results demonstrate that the bioinspired multifunctional CuS-Fn NCs have potential as clinically translatable cancer theranostics and could provide a noninvasive, highly sensitive, and quantitative in vivo guiding method for cancer photothermal therapies in experimental and clinical settings.
authors.affiliation: State Key Laboratory of Molecular Vaccinology and Molecular Diagnostics & Center for Molecular Imaging and Translational Medicine, School of Public Health, Xiamen University , Xiamen 361102, China.
authors.forename: Zhantong
authors.initials: Z
authors.lastname: Wang
authors.affiliation: Guangdong Key Laboratory for Biomedical Measurements and Ultrasound Imaging, Department of Biomedical Engineering, School of Medicine, Shenzhen University , Shenzhen 518060, China.
authors.forename: Peng
authors.initials: P
authors.lastname: Huang
authors.affiliation: Laboratory of Molecular Imaging and Nanomedicine, National Institute of Biomedical Imaging and Bioengineering, National Institutes of Health , Bethesda, Maryland 20892, United States.
authors.forename: Orit
authors.initials: O
authors.lastname: Jacobson
authors.affiliation: Laboratory of Molecular Imaging and Nanomedicine, National Institute of Biomedical Imaging and Bioengineering, National Institutes of Health , Bethesda, Maryland 20892, United States.
authors.forename: Zhe
authors.initials: Z
authors.lastname: Wang
authors.affiliation: Laboratory of Molecular Imaging and Nanomedicine, National Institute of Biomedical Imaging and Bioengineering, National Institutes of Health , Bethesda, Maryland 20892, United States.
authors.forename: Yijing
authors.initials: Y
authors.lastname: Liu
authors.affiliation: Laboratory of Molecular Imaging and Nanomedicine, National Institute of Biomedical Imaging and Bioengineering, National Institutes of Health , Bethesda, Maryland 20892, United States.
authors.forename: Lisen
authors.initials: L
authors.lastname: Lin
authors.affiliation: Guangdong Key Laboratory for Biomedical Measurements and Ultrasound Imaging, Department of Biomedical Engineering, School of Medicine, Shenzhen University , Shenzhen 518060, China.
authors.forename: Jing
authors.initials: J
authors.lastname: Lin
authors.affiliation: Laboratory of Molecular Imaging and Nanomedicine, National Institute of Biomedical Imaging and Bioengineering, National Institutes of Health , Bethesda, Maryland 20892, United States.
authors.forename: Nan
authors.initials: N
authors.lastname: Lu
authors.affiliation: Laboratory of Molecular Imaging and Nanomedicine, National Institute of Biomedical Imaging and Bioengineering, National Institutes of Health , Bethesda, Maryland 20892, United States.
authors.forename: Huimin
authors.initials: H
authors.lastname: Zhang
authors.affiliation: State Key Laboratory of Molecular Vaccinology and Molecular Diagnostics & Center for Molecular Imaging and Translational Medicine, School of Public Health, Xiamen University , Xiamen 361102, China.|Laboratory of Molecular Imaging and Nanomedicine, National Institute of Biomedical Imaging and Bioengineering, National Institutes of Health , Bethesda, Maryland 20892, United States.
authors.forename: Rui
authors.initials: R
authors.lastname: Tian
authors.affiliation: Laboratory of Molecular Imaging and Nanomedicine, National Institute of Biomedical Imaging and Bioengineering, National Institutes of Health , Bethesda, Maryland 20892, United States.
authors.forename: Gang
authors.initials: G
authors.lastname: Niu
authors.affiliation: State Key Laboratory of Molecular Vaccinology and Molecular Diagnostics & Center for Molecular Imaging and Translational Medicine, School of Public Health, Xiamen University , Xiamen 361102, China.
authors.forename: Gang
authors.initials: G
authors.lastname: Liu
authors.affiliation: Laboratory of Molecular Imaging and Nanomedicine, National Institute of Biomedical Imaging and Bioengineering, National Institutes of Health , Bethesda, Maryland 20892, United States.
authors.forename: Xiaoyuan
authors.initials: X
authors.lastname: Chen
mesh_terms: D000818:Animals; D032701:Biomimetics; D045744:Cell Line, Tumor; D003300:Copper / Q000737:chemistry* / Q000627:therapeutic use*; D005293:Ferritins / Q000737:chemistry* / Q000627:therapeutic use*; D006801:Humans; D006979:Hyperthermia, Induced; D008819:Mice, Nude; D009369:Neoplasms / Q000000981:diagnostic imaging* / Q000473:pathology / Q000628:therapy*; D061088:Photoacoustic Techniques; D010789:Phototherapy; D049268:Positron-Emission Tomography; D000068936:Theranostic Nanomedicine
chemical_list: D003300:Copper; D005293:Ferritins; C017846:cupric sulfide
keywords: CuS; PET; biomimetic synthesis; ferritin; photoacoustic imaging; photothermal therapy