A Mn(III)-Sealed Metal-Organic Framework Nanosystem for Redox-Unlocked Tumor Theranostics.

Here, a Mn(III)-sealed metal-organic framework (MOF) nanosystem based on coordination between Mn(III) and porphyrin (TCPP) via a one-pot method was designed and constructed. Mn(III), as a sealer, not only quenched TCPP-based fluorescence but also inhibited reactive oxygen species (ROS) generation, which made MOFs an "inert" theranostic nanoparticle. Interestingly, upon endocytosis by tumor cells, MOFs were disintegrated into Mn(II) and free TCPP by intracellular glutathione (GSH) in tumor cells, owing to redox reaction between Mn(III) and GSH. This disintegration would lead to consumption of antioxidant GSH and activated Mn(II)-based magnetic resonance imaging (MRI) as well as TCPP-based fluorescent imaging. More importantly, such a GSH-regulated TCPP release could implement controllable ROS generation under irradiation, which avoided side effects (inflammation and damage of normal tissues). As a consequence, after unlocking by GSH, Mn(III)-sealed MOFs could significantly improve the therapeutic efficiency of photodynamic therapy by combining controlled ROS generation and GSH depletion after precise dual tumor homing.

[1]  Xian‐Zheng Zhang,et al.  Structural Transformation in Metal-Organic Frameworks for Reversible Binding of Oxygen. , 2019, Angewandte Chemie.

[2]  Xuexiang Han,et al.  Biomimetic Metal–Organic Framework Nanoparticles for Cooperative Combination of Antiangiogenesis and Photodynamic Therapy for Enhanced Efficacy , 2019, Advanced materials.

[3]  Shuang‐Shuang Wan,et al.  An ATP-Regulated Ion Transport Nanosystem for Homeostatic Perturbation Therapy and Sensitizing Photodynamic Therapy by Autophagy Inhibition of Tumors , 2019, ACS central science.

[4]  Yuanzhi Tang,et al.  Effect of Manganese Oxide Aging and Structure Transformation on the Kinetics of Thiol Oxidation. , 2018, Environmental science & technology.

[5]  Yang Song,et al.  Nanoscale metal-organic frameworks for mitochondria-targeted radiotherapy-radiodynamic therapy , 2018, Nature Communications.

[6]  W. Cai,et al.  Photo-Enhanced Singlet Oxygen Generation of Prussian Blue-Based Nanocatalyst for Augmented Photodynamic Therapy , 2018, iScience.

[7]  Jin‐Yue Zeng,et al.  ROS-induced NO generation for gas therapy and sensitizing photodynamic therapy of tumor. , 2018, Biomaterials.

[8]  F. Huang,et al.  Ferric metal-organic framework for microwave absorption , 2018, Materials Today Chemistry.

[9]  Hui Zhang,et al.  Theranostic Mn-Porphyrin Metal-Organic Frameworks for Magnetic Resonance Imaging-Guided Nitric Oxide and Photothermal Synergistic Therapy. , 2018, ACS applied materials & interfaces.

[10]  Jun Lin,et al.  Tumor Microenvironment‐Responsive Mesoporous MnO2‐Coated Upconversion Nanoplatform for Self‐Enhanced Tumor Theranostics , 2018, Advanced Functional Materials.

[11]  Xiaoping Zhou,et al.  Improved Stable Indocyanine Green (ICG)‐Mediated Cancer Optotheranostics with Naturalized Hepatitis B Core Particles , 2018, Advanced materials.

[12]  Ping Li,et al.  Enhanced Photodynamic Therapy by Reduced Levels of Intracellular Glutathione Obtained By Employing a Nano-MOF with CuII as the Active Center. , 2018, Angewandte Chemie.

[13]  Juan Li,et al.  Simultaneous Fenton-like Ion Delivery and Glutathione Depletion by MnO2 -Based Nanoagent to Enhance Chemodynamic Therapy. , 2018, Angewandte Chemie.

[14]  Qianwang Chen,et al.  In Situ One‐Pot Synthesis of MOF–Polydopamine Hybrid Nanogels with Enhanced Photothermal Effect for Targeted Cancer Therapy , 2018, Advanced science.

[15]  Xian‐Zheng Zhang,et al.  π-Extended Benzoporphyrin-Based Metal-Organic Framework for Inhibition of Tumor Metastasis. , 2018, ACS nano.

[16]  R. Zhao,et al.  Enzyme-MOF Nanoreactor Activates Nontoxic Paracetamol for Cancer Therapy. , 2018, Angewandte Chemie.

[17]  Xiaoyuan Chen,et al.  Organic Semiconducting Photoacoustic Nanodroplets for Laser-Activatable Ultrasound Imaging and Combinational Cancer Therapy. , 2018, ACS nano.

[18]  Mengyun Peng,et al.  Porphyrinic Metal–Organic Frameworks Coated Gold Nanorods as a Versatile Nanoplatform for Combined Photodynamic/Photothermal/Chemotherapy of Tumor , 2018 .

[19]  Wenlong Cheng,et al.  A Facile Ion-Doping Strategy To Regulate Tumor Microenvironments for Enhanced Multimodal Tumor Theranostics. , 2018, Journal of the American Chemical Society.

[20]  Bo Tang,et al.  H2 S-Activable MOF Nanoparticle Photosensitizer for Effective Photodynamic Therapy against Cancer with Controllable Singlet-Oxygen Release. , 2017, Angewandte Chemie.

[21]  Fan Gao,et al.  Initiator-Loaded Gold Nanocages as a Light-Induced Free-Radical Generator for Cancer Therapy. , 2017, Angewandte Chemie.

[22]  D. Aurbach,et al.  On the Oxidation State of Manganese Ions in Li-Ion Battery Electrolyte Solutions. , 2017, Journal of the American Chemical Society.

[23]  Zhuang Liu,et al.  Emerging nanomedicine approaches fighting tumor metastasis: animal models, metastasis-targeted drug delivery, phototherapy, and immunotherapy. , 2016, Chemical Society reviews.

[24]  Huijuan Wang,et al.  Controllable synthesis of dual-MOFs nanostructures for pH-responsive artemisinin delivery, magnetic resonance and optical dual-model imaging-guided chemo/photothermal combinational cancer therapy. , 2016, Biomaterials.

[25]  Jihye Park,et al.  Size-Controlled Synthesis of Porphyrinic Metal-Organic Framework and Functionalization for Targeted Photodynamic Therapy. , 2016, Journal of the American Chemical Society.

[26]  Demin Liu,et al.  Nanomedicine Applications of Hybrid Nanomaterials Built from Metal-Ligand Coordination Bonds: Nanoscale Metal-Organic Frameworks and Nanoscale Coordination Polymers. , 2015, Chemical reviews.

[27]  Z. Yin,et al.  Real-time monitoring of arsenic trioxide release and delivery by activatable T(1) imaging. , 2015, ACS nano.

[28]  Zhe Wang,et al.  Early-Stage Imaging of Nanocarrier-Enhanced Chemotherapy Response in Living Subjects by Scalable Photoacoustic Microscopy , 2014, ACS nano.

[29]  Wenbin Lin,et al.  Nanoscale Metal–Organic Framework for Highly Effective Photodynamic Therapy of Resistant Head and Neck Cancer , 2014, Journal of the American Chemical Society.

[30]  Ick Chan Kwon,et al.  Nanophotosensitizers toward advanced photodynamic therapy of Cancer. , 2013, Cancer letters.

[31]  Young‐Tae Chang,et al.  Intracellular glutathione detection using MnO(2)-nanosheet-modified upconversion nanoparticles. , 2011, Journal of the American Chemical Society.

[32]  Andrea R. Gerson,et al.  Resolving surface chemical states in XPS analysis of first row transition metals, oxides and hydroxides: Sc, Ti, V, Cu and Zn , 2010 .

[33]  Irving L. Weissman,et al.  Association of reactive oxygen species levels and radioresistance in cancer stem cells , 2009, Nature.

[34]  Michael R Hamblin,et al.  Photodynamic therapy and anti-tumour immunity , 2006, Nature Reviews Cancer.

[35]  R. Jain,et al.  Photodynamic therapy for cancer , 2003, Nature Reviews Cancer.