title: Dual-Stimuli Responsive Nanotheranostics for Multimodal Imaging Guided Trimodal Synergistic Therapy.
abstract: Multimodal imaging guided synergistic therapy promises more accurate diagnosis than any single imaging modality, and higher therapeutic efficiency than any single one or their simple "mechanical" combination. Herein, we report a dual-stimuli responsive nanotheranostic based on a hierarchical nanoplatform, composed of mesoporous silica-coated gold nanorods (GNR@SiO2), Indocyanine Green (ICG), and 5-fluorouracil (5-FU), for in vivo multimodal imaging guided synergistic therapy. The 5-FU loaded ICG-conjugated silica-coated gold nanorods (GNR@SiO2-5-FU-ICG) was able to response specifically to the two stimuli of pH change and near-infrared (NIR) light irradiation. Both the NIR light irradiation and acidic environment accelerated the 5-FU release. Meanwhile, the heat generation and singlet oxygen production can be induced by GNR@SiO2-5-FU-ICG upon light irradiation. Most intriguingly, the nanoplatform also promises multimodal imaging such as two-photon luminescence, fluorescence, photoacoustic, photothermal imaging, as well as trimodal synergistic therapy such as photothermal therapy (PTT), photodynamic therapy (PDT), and chemotherapy. The cancer theranostic capability of GNR@SiO2-5-FU-ICG was evaluated both in vitro and in vivo. The trimodal synergistic therapy with the guidance of multimodal imaging exhibited remarkably enhanced treatment efficacy. This concept of a hierarchical nanoplatform integrates multiple diagnostic/therapeutic modalities into one platform, which can potentially be applied as personalized nanomedicine with drug delivery, diagnosis, and treatment.
authors.affiliation: Department of Dermatology and Venereology, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, Zhejiang, 325000, China.|Department of Dermatology and Venereology, The Second Affiliated Hospital of Wenzhou Medical University, Wenzhou, Zhejiang, 325000, China.
authors.forename: Shan
authors.initials: S
authors.lastname: Fang
authors.affiliation: Guangdong Key Laboratory for Biomedical Measurements and Ultrasound Imaging, School of Biomedical Engineering, Shenzhen University, Shenzhen, 518060, China.
authors.forename: Jing
authors.initials: J
authors.lastname: Lin
authors.affiliation: Department of Dermatology and Venereology, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, Zhejiang, 325000, China.
authors.forename: Chunxiao
authors.initials: C
authors.lastname: Li
authors.affiliation: Guangdong Key Laboratory for Biomedical Measurements and Ultrasound Imaging, School of Biomedical Engineering, Shenzhen University, Shenzhen, 518060, China.
authors.forename: Peng
authors.initials: P
authors.lastname: Huang
authors.affiliation: Department of Bio-Nano Science and Engineering, Key Laboratory for Thin Film and Microfabrication of Ministry of Education, Research Institute of Micro/Nano Science and Technology, Shanghai Jiao Tong University, Shanghai, 200240, China.
authors.forename: Wenxiu
authors.initials: W
authors.lastname: Hou
authors.affiliation: Department of Bio-Nano Science and Engineering, Key Laboratory for Thin Film and Microfabrication of Ministry of Education, Research Institute of Micro/Nano Science and Technology, Shanghai Jiao Tong University, Shanghai, 200240, China.
authors.forename: Chunlei
authors.initials: C
authors.lastname: Zhang
authors.affiliation: Department of Dermatology and Venereology, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, Zhejiang, 325000, China.
authors.forename: Jingjing
authors.initials: J
authors.lastname: Liu
authors.affiliation: Department of Dermatology and Venereology, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, Zhejiang, 325000, China.
authors.forename: Sisi
authors.initials: S
authors.lastname: Huang
authors.affiliation: Guangdong Key Laboratory for Biomedical Measurements and Ultrasound Imaging, School of Biomedical Engineering, Shenzhen University, Shenzhen, 518060, China.
authors.forename: Yongxiang
authors.initials: Y
authors.lastname: Luo
authors.affiliation: Guangdong Key Laboratory for Biomedical Measurements and Ultrasound Imaging, School of Biomedical Engineering, Shenzhen University, Shenzhen, 518060, China.
authors.forename: Wenpei
authors.initials: W
authors.lastname: Fan
authors.affiliation: Department of Bio-Nano Science and Engineering, Key Laboratory for Thin Film and Microfabrication of Ministry of Education, Research Institute of Micro/Nano Science and Technology, Shanghai Jiao Tong University, Shanghai, 200240, China.
authors.forename: Daxiang
authors.initials: D
authors.lastname: Cui
authors.affiliation: Department of Dermatology and Venereology, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, Zhejiang, 325000, China.
authors.forename: Yunsheng
authors.initials: Y
authors.lastname: Xu
authors.affiliation: Department of Dermatology and Venereology, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, Zhejiang, 325000, China.
authors.forename: Zhiming
authors.initials: Z
authors.lastname: Li
mesh_terms: D000818:Animals; D016923:Cell Death / Q000187:drug effects; D045744:Cell Line, Tumor; D003131:Combined Modality Therapy; D065546:Drug Liberation; D005472:Fluorouracil / Q000494:pharmacology; D006046:Gold / Q000737:chemistry; D006801:Humans; D006863:Hydrogen-Ion Concentration; D007208:Indocyanine Green / Q000494:pharmacology; D051379:Mice; D008856:Microscopy, Fluorescence; D064847:Multimodal Imaging; D050997:Nanomedicine / Q000379:methods*; D043942:Nanotubes / Q000648:ultrastructure; D017785:Photons; D012822:Silicon Dioxide / Q000737:chemistry; D000068936:Theranostic Nanomedicine / Q000379:methods*
chemical_list: D006046:Gold; D012822:Silicon Dioxide; D007208:Indocyanine Green; D005472:Fluorouracil
keywords: light-controlled drug release; multimodal imaging; pH-responsive drug release; silica-coated gold nanorods; theranostics; trimodal synergistic therapy