Cell Membrane Coated Semiconducting Polymer Nanoparticles for Enhanced Multimodal Cancer Phototheranostics.

Phototheranostic nanoagents are promising for early diagnosis and precision therapy of cancer. However, their imaging ability and therapeutic efficacy are often limited due to the presence of delivery barriers in the tumor microenvironment. Herein, we report the development of organic multimodal phototheranostic nanoagents that can biomimetically target cancer-associated fibroblasts in the tumor microenvironment for enhanced multimodal imaging-guided cancer therapy. Such biomimetic nanocamouflages comprise a near-infrared (NIR) absorbing semiconducting polymer nanoparticle (SPN) coated with the cell membranes of activated fibroblasts. The homologous targeting mechanism allows the activated fibroblast cell membrane coated SPN (AF-SPN) to specifically target cancer-associated fibroblasts, leading to enhanced tumor accumulation relative to the uncoated and cancer cell membrane coated counterparts after systemic administration in living mice. As such, AF-SPN not only provides stronger NIR fluorescence and photoacoustic signals to detect tumors but also generates enhanced cytotoxic heat and singlet oxygen to exert combinational photothermal and photodynamic therapy, ultimately leading to an antitumor efficacy higher than that of the counterparts. This study introduces an organic phototheranostic system that biomimetically targets the component in the tumor microenvironment for enhanced multimodal cancer theranostics.

[1]  Mahdi Karimi,et al.  Smart Nanostructures for Cargo Delivery: Uncaging and Activating by Light. , 2017, Journal of the American Chemical Society.

[2]  Jonathan C Irish,et al.  A PEGylation-Free Biomimetic Porphyrin Nanoplatform for Personalized Cancer Theranostics. , 2015, ACS nano.

[3]  Jian Zhang,et al.  Highly absorbing multispectral near-infrared polymer nanoparticles from one conjugated backbone for photoacoustic imaging and photothermal therapy. , 2017, Biomaterials.

[4]  Kai Yang,et al.  Activatable hyaluronic acid nanoparticle as a theranostic agent for optical/photoacoustic image-guided photothermal therapy. , 2014, ACS nano.

[5]  Xingzhong Zhao,et al.  Antitumor Platelet‐Mimicking Magnetic Nanoparticles , 2017 .

[6]  J. Eriksson,et al.  Targeted intracellular delivery of hydrophobic agents using mesoporous hybrid silica nanoparticles as carrier systems. , 2009, Nano letters.

[7]  W. Cai,et al.  Reassembly of 89Zr‐Labeled Cancer Cell Membranes into Multicompartment Membrane‐Derived Liposomes for PET‐Trackable Tumor‐Targeted Theranostics , 2018, Advanced materials.

[8]  W. Liu,et al.  Platelet-Facilitated Photothermal Therapy of Head and Neck Squamous Cell Carcinoma. , 2018, Angewandte Chemie.

[9]  Dan Ding,et al.  Regulating Near-Infrared Photodynamic Properties of Semiconducting Polymer Nanotheranostics for Optimized Cancer Therapy. , 2017, ACS nano.

[10]  Jianlin Shi,et al.  Chemical Design and Synthesis of Functionalized Probes for Imaging and Treating Tumor Hypoxia. , 2017, Chemical reviews.

[11]  Jianghong Rao,et al.  Recent progress on semiconducting polymer nanoparticles for molecular imaging and cancer phototherapy. , 2018, Biomaterials.

[12]  B. Tang,et al.  One-Step Formulation of Targeted Aggregation-Induced Emission Dots for Image-Guided Photodynamic Therapy of Cholangiocarcinoma. , 2017, ACS nano.

[13]  Mingyuan Gao,et al.  Enhancing Both Biodegradability and Efficacy of Semiconducting Polymer Nanoparticles for Photoacoustic Imaging and Photothermal Therapy. , 2018, ACS nano.

[14]  Peng Yang,et al.  Red blood cell membrane-camouflaged melanin nanoparticles for enhanced photothermal therapy. , 2017, Biomaterials.

[15]  T. Ji,et al.  Peptide Assembly Integration of Fibroblast‐Targeting and Cell‐Penetration Features for Enhanced Antitumor Drug Delivery , 2015, Advanced materials.

[16]  Liangzhu Feng,et al.  Hyaluronidase To Enhance Nanoparticle-Based Photodynamic Tumor Therapy. , 2016, Nano letters.

[17]  Christian Wiraja,et al.  Near-Infrared Fluorescent Molecular Probe for Sensitive Imaging of Keloid. , 2018, Angewandte Chemie.

[18]  D. Zheng,et al.  Preferential Cancer Cell Self-Recognition and Tumor Self-Targeting by Coating Nanoparticles with Homotypic Cancer Cell Membranes. , 2016, Nano letters.

[19]  Zhen Gu,et al.  Engineered Nanoplatelets for Enhanced Treatment of Multiple Myeloma and Thrombus , 2016, Advanced materials.

[20]  Brandon S. Brown,et al.  Bromelain Surface Modification Increases the Diffusion of Silica Nanoparticles in the Tumor Extracellular Matrix , 2014, ACS nano.

[21]  Daniel T Chiu,et al.  Highly fluorescent semiconducting polymer dots for biology and medicine. , 2013, Angewandte Chemie.

[22]  Chenyao Wu,et al.  Bottom-up synthesis of WS2 nanosheets with synchronous surface modification for imaging guided tumor regression. , 2017, Acta biomaterialia.

[23]  Y. Liu,et al.  Cell Membrane Camouflaged Hollow Prussian Blue Nanoparticles for Synergistic Photothermal‐/Chemotherapy of Cancer , 2017 .

[24]  Zhen Gu,et al.  Anticancer Platelet‐Mimicking Nanovehicles , 2015, Advanced materials.

[25]  Xu Zhen,et al.  Intraparticle Energy Level Alignment of Semiconducting Polymer Nanoparticles to Amplify Chemiluminescence for Ultrasensitive In Vivo Imaging of Reactive Oxygen Species. , 2016, ACS nano.

[26]  Xiaofei Wang,et al.  Red blood cell membrane camouflaged magnetic nanoclusters for imaging-guided photothermal therapy. , 2016, Biomaterials.

[27]  Ping Gong,et al.  Cancer Cell Membrane-Biomimetic Nanoparticles for Homologous-Targeting Dual-Modal Imaging and Photothermal Therapy. , 2016, ACS nano.

[28]  Tianyue Jiang,et al.  Tumor Microenvironment-Mediated Construction and Deconstruction of Extracellular Drug-Delivery Depots. , 2016, Nano letters.

[29]  Peng Chen,et al.  Oxygenic Hybrid Semiconducting Nanoparticles for Enhanced Photodynamic Therapy. , 2018, Nano letters.

[30]  Xian‐Zheng Zhang,et al.  A biomimetic theranostic O2-meter for cancer targeted photodynamic therapy and phosphorescence imaging. , 2018, Biomaterials.

[31]  Kanyi Pu,et al.  Reaction-Based Semiconducting Polymer Nanoprobes for Photoacoustic Imaging of Protein Sulfenic Acids. , 2017, ACS nano.

[32]  Hongwei Duan,et al.  Dendronized Semiconducting Polymer as Photothermal Nanocarrier for Remote Activation of Gene Expression. , 2017, Angewandte Chemie.

[33]  Chao Wang,et al.  Erythrocyte‐Membrane‐Enveloped Perfluorocarbon as Nanoscale Artificial Red Blood Cells to Relieve Tumor Hypoxia and Enhance Cancer Radiotherapy , 2017, Advanced materials.

[34]  Wei Wei,et al.  Cancer Cell Membrane-Biomimetic Nanoprobes with Two-Photon Excitation and Near-Infrared Emission for Intravital Tumor Fluorescence Imaging. , 2018, ACS nano.

[35]  Chengbo Liu,et al.  Indocyanine Green-holo-Transferrin Nanoassemblies for Tumor-Targeted Dual-Modal Imaging and Photothermal Therapy of Glioma. , 2017, ACS applied materials & interfaces.

[36]  Qiong Yang,et al.  Water-soluble conjugated polymers for imaging, diagnosis, and therapy. , 2012, Chemical reviews.

[37]  Dong Mei,et al.  Comprehensively priming the tumor microenvironment by cancer-associated fibroblast-targeted liposomes for combined therapy with cancer cell-targeted chemotherapeutic drug delivery system. , 2016, Journal of controlled release : official journal of the Controlled Release Society.

[38]  Kanyi Pu,et al.  Semiconducting Polymer Nanoenzymes with Photothermic Activity for Enhanced Cancer Therapy. , 2018, Angewandte Chemie.

[39]  Xiu‐Ping Yan,et al.  Dual-stimuli responsive and reversibly activatable theranostic nanoprobe for precision tumor-targeting and fluorescence-guided photothermal therapy , 2017, Nature Communications.

[40]  Song Shen,et al.  Spatial Targeting of Tumor-Associated Macrophages and Tumor Cells with a pH-Sensitive Cluster Nanocarrier for Cancer Chemoimmunotherapy. , 2017, Nano letters.

[41]  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.

[42]  Shengliang Li,et al.  Photothermal‐Responsive Conjugated Polymer Nanoparticles for Remote Control of Gene Expression in Living Cells , 2018, Advanced materials.

[43]  Pengcheng Zhang,et al.  Cancer‐Cell‐Biomimetic Nanoparticles for Targeted Therapy of Homotypic Tumors , 2016, Advanced materials.

[44]  Xu Zhen,et al.  Dual‐Peak Absorbing Semiconducting Copolymer Nanoparticles for First and Second Near‐Infrared Window Photothermal Therapy: A Comparative Study , 2018, Advanced materials.

[45]  Kanyi Pu,et al.  Nanoparticle Regrowth Enhances Photoacoustic Signals of Semiconducting Macromolecular Probe for In Vivo Imaging , 2017, Advanced materials.

[46]  Paul Kumar Upputuri,et al.  Broadband Absorbing Semiconducting Polymer Nanoparticles for Photoacoustic Imaging in Second Near-Infrared Window. , 2017, Nano letters.

[47]  Yuyan Jiang,et al.  Advanced Photoacoustic Imaging Applications of Near-Infrared Absorbing Organic Nanoparticles. , 2017, Small.

[48]  Yaping Li,et al.  Long Circulation Red‐Blood‐Cell‐Mimetic Nanoparticles with Peptide‐Enhanced Tumor Penetration for Simultaneously Inhibiting Growth and Lung Metastasis of Breast Cancer , 2016, Advanced Functional Materials.

[49]  Ronnie H. Fang,et al.  Cell Membrane Coating Nanotechnology , 2018, Advanced materials.

[50]  Jesse V Jokerst,et al.  Molecular afterglow imaging with bright, biodegradable polymer nanoparticles , 2017, Nature Biotechnology.

[51]  Yan Lyu,et al.  Semiconducting Polymer Nanobioconjugates for Targeted Photothermal Activation of Neurons. , 2016, Journal of the American Chemical Society.

[52]  Xinglu Jiang,et al.  Plasmon-mediated generation of reactive oxygen species from near-infrared light excited gold nanocages for photodynamic therapy in vitro. , 2014, ACS nano.

[53]  R. Kalluri.  The biology and function of fibroblasts in cancer , 2016, Nature Reviews Cancer.

[54]  Yanglong Hou,et al.  Multifunctional Fe5C2 Nanoparticles: A Targeted Theranostic Platform for Magnetic Resonance Imaging and Photoacoustic Tomography‐Guided Photothermal Therapy , 2014, Advanced materials.

[55]  Jie Yu,et al.  High-throughput synthesis of single-layer MoS2 nanosheets as a near-infrared photothermal-triggered drug delivery for effective cancer therapy. , 2014, ACS nano.

[56]  Pengcheng Zhang,et al.  Enhanced Blood Suspensibility and Laser-Activated Tumor-specific Drug Release of Theranostic Mesoporous Silica Nanoparticles by Functionalizing with Erythrocyte Membranes , 2017, Theranostics.

[57]  D. Jaffray,et al.  Radiation effects on the tumor microenvironment: Implications for nanomedicine delivery☆ , 2017, Advanced drug delivery reviews.

[58]  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.

[59]  S. Gambhir,et al.  Nanomaterials for In Vivo Imaging. , 2017, Chemical reviews.

[60]  Xiaoqi Sun,et al.  Cancer Cell Membrane-Coated Adjuvant Nanoparticles with Mannose Modification for Effective Anticancer Vaccination. , 2018, ACS nano.

[61]  Zhiguang Wu,et al.  Stem-Cell-Membrane Camouflaging on Near-Infrared Photoactivated Upconversion Nanoarchitectures for in Vivo Remote-Controlled Photodynamic Therapy. , 2016, ACS applied materials & interfaces.