Porous SiO2-Based Reactor with Self-Supply of O2 and H2O2 for Synergistic Photo-Thermal/Photodynamic Therapy

Purpose Although the combined photo-thermal (PTT) and photodynamic therapy (PDT) of tumors have demonstrated promise as effective cancer therapy, the hypoxic and insufficient H2O2 supply of tumors seriously limits the efficacy of PDT, and the acidic environment reduces the catalytic activity of nanomaterial in the tumor microenvironment. To develop a platform for efficiently addressing these challenges, we constructed a nanomaterial of Aptamer@dox/GOD-MnO2-SiO2@HGNs-Fc@Ce6 (AMS) for combination tumor therapy. The treatment effects of AMS were evaluated both in vitro and in vivo. Methods In this work, Ce6 and hemin were loaded on graphene (GO) through π-π conjugation, and Fc was connected to GO via amide bond. The HGNs-Fc@Ce6 was loaded into SiO2, and coated with dopamine. Then, MnO2 was modified on the SiO2. Finally, AS1411-aptamer@dox and GOD were fixed to gain AMS. We characterized the morphology, size, and zeta potential of AMS. The oxygen and reactive oxygen species (ROS) production properties of AMS were analyzed. The cytotoxicity of AMS was detected by MTT and calcein-AM/PI assays. The apoptosis of AMS to a tumor cell was estimated with a JC-1 probe, and the ROS level was detected with a 2’,7’-Dichlorodihydrofluorescein diacetate (DCFH-DA) probe. The anticancer efficacy in vivo was analyzed by the changes in the tumor size in different treatment groups. Results AMS was targeted to the tumor cell and released doxorubicin. It decomposed glucose to produce H2O2 in the GOD-mediated reaction. The generated sufficient H2O2 was catalyzed by MnO2 and HGNs-Fc@Ce6 to produce O2 and free radicals (•OH), respectively. The increased oxygen content improved the hypoxic environment of the tumor and effectively reduced the resistance to PDT. The generated •OH enhanced the ROS treatment. Moreover, AMS depicted a good photo-thermal effect. Conclusion The results revealed that AMS had an excellent enhanced therapy effect by combining synergistic PTT and PDT.

[1]  Z. Dai,et al.  NIR light-driven photocatalytic NAD(P)H oxidation and H2O2 generation in situ for enhanced chemodynamic therapy and immune response , 2023, Nano Today.

[2]  Lei Zhao,et al.  Disulfide-Bridged Dendritic Organosilicas-Based Biodegradable Molecularly Imprinted Polymers for Multiple Targeting and pH/Redox-responsive Drug Release Toward Chemical/Photodynamic Synergistic Tumor Therapy. , 2023, Advanced Healthcare Materials.

[3]  Yafei Wu,et al.  Amorphous NiB@IrOx nanozymes trigger efficient apoptosis-ferroptosis hybrid therapy. , 2022, Acta biomaterialia.

[4]  Fenglei Gao,et al.  Smart PdH@MnO2 Yolk-Shell Nanostructures for Spatiotemporally Synchronous Targeted Hydrogen Delivery and Oxygen-Elevated Phototherapy of Melanoma. , 2022, ACS nano.

[5]  Y. Wang,et al.  Multitarget Reaction Programmable Automatic Diagnosis and Treatment Logic Device. , 2021, ACS nano.

[6]  Yuheng Wang,et al.  Hypoxia-responsive block copolymer polyprodrugs for complementary photodynamic-chemotherapy. , 2021, Journal of controlled release : official journal of the Controlled Release Society.

[7]  Jianxiu Wang,et al.  MoO3-x nanosheets-based platform for single NIR laser induced efficient PDT/PTT of cancer. , 2021, Journal of controlled release : official journal of the Controlled Release Society.

[8]  R. Pei,et al.  Synthesis of Au@MOF core-shell hybrids for enhanced photodynamic/photothermal therapy. , 2021, Journal of materials chemistry. B.

[9]  Yun Yang,et al.  Anisotropic Truncated Octahedral Au with Pt Deposition on Arris for Localized Surface Plasmon Resonance-Enhanced Photothermal and Photodynamic Therapy of Osteosarcoma. , 2021, ACS applied materials & interfaces.

[10]  Y. Duan,et al.  Immune/Hypoxic Tumor Microenvironment Regulation-Enhanced Photodynamic Treatment Realized by pH-Responsive Phase Transition-Targeting Nanobubbles. , 2021, ACS applied materials & interfaces.

[11]  Chulgyu Song,et al.  Tumor-Targeting H2O2-Responsive Photosensitizing Nanoparticles with Antiangiogenic and Immunogenic Activities for Maximizing Anticancer Efficacy of Phototherapy. , 2021, ACS applied bio materials.

[12]  Jianping Zhou,et al.  Hypoxia-Sensitive Zwitterionic Vehicle for Tumor-Specific Drug Delivery through Antifouling-Based Stable Biotransport Alongside PDT-Sensitized Controlled Release. , 2021, Biomacromolecules.

[13]  Yun Sun,et al.  Plasma membrane targeted photodynamic O2 economizer for hypoxic tumor therapy. , 2021, Biomaterials.

[14]  Jing Lin,et al.  Biomimetic nanoemulsion for synergistic photodynamic-immunotherapy against hypoxic breast tumor. , 2021, Angewandte Chemie.

[15]  F. Greten,et al.  Immune cell - produced ROS and their impact on tumor growth and metastasis , 2021, Redox biology.

[16]  Yingchun Zhu,et al.  Activatable nanomedicine for overcoming hypoxia-induced resistance to chemotherapy and inhibiting tumor growth by inducing collaborative apoptosis and ferroptosis in solid tumors. , 2020, Biomaterials.

[17]  Daozhen Chen,et al.  Enhancement of tumor lethality of ROS in photodynamic therapy , 2020, Cancer medicine.

[18]  Xian‐Zheng Zhang,et al.  Free radicals for cancer theranostics. , 2020, Biomaterials.

[19]  Z. Xu,et al.  Sequential PDT and PTT Using Dual‐Modal Single‐Walled Carbon Nanohorns Synergistically Promote Systemic Immune Responses against Tumor Metastasis and Relapse , 2020, Advanced science.

[20]  J. Park,et al.  Hypoxia-responsive nanoparticles for tumor-targeted drug delivery. , 2020, Cancer letters.

[21]  Jun Lin,et al.  Au2Pt-PEG-Ce6 nanoformulation with dual nanozyme activities for synergistic chemodynamic therapy / phototherapy. , 2020, Biomaterials.

[22]  Dean P. Jones,et al.  Reactive oxygen species (ROS) as pleiotropic physiological signalling agents , 2020, Nature Reviews Molecular Cell Biology.

[23]  Bifeng Liu,et al.  Activating Antitumor Immunity and Antimetastatic Effect Through Polydopamine‐Encapsulated Core–Shell Upconversion Nanoparticles , 2019, Advanced materials.

[24]  Jingqing Yang,et al.  Targeting photodynamic and photothermal therapy to the endoplasmic reticulum enhances immunogenic cancer cell death , 2019, Nature Communications.

[25]  J. Fei,et al.  Nanozyme-Catalyzed Cascade Reactions for Mitochondria-Mimicking Oxidative Phosphorylation. , 2019, Angewandte Chemie.

[26]  Kai Yang,et al.  Holo-Lactoferrin Modified Liposome for Relieving Tumor Hypoxia and Enhancing Radiochemotherapy of Cancer. , 2019, Small.

[27]  A. Jeyasekharan,et al.  ROS and the DNA damage response in cancer , 2018, Redox biology.

[28]  Zhuang Liu,et al.  Tumor-pH-Responsive Dissociable Albumin-Tamoxifen Nanocomplexes Enabling Efficient Tumor Penetration and Hypoxia Relief for Enhanced Cancer Photodynamic Therapy. , 2018, Small.

[29]  G. Jiang,et al.  Nanoparticle‐based photothermal and photodynamic immunotherapy for tumor treatment , 2018, International journal of cancer.

[30]  Juyoung Yoon,et al.  Innovative Strategies for Hypoxic-Tumor Photodynamic Therapy. , 2018, Angewandte Chemie.

[31]  Lanlan Liu,et al.  Tumor-targeted hybrid protein oxygen carrier to simultaneously enhance hypoxia-dampened chemotherapy and photodynamic therapy at a single dose , 2018, Theranostics.

[32]  C. Supuran,et al.  pH-Sensitive Multiligand Gold Nanoplatform Targeting Carbonic Anhydrase IX Enhances the Delivery of Doxorubicin to Hypoxic Tumor Spheroids and Overcomes the Hypoxia-Induced Chemoresistance. , 2018, ACS applied materials & interfaces.

[33]  Zhuang Liu,et al.  Hollow MnO2 as a tumor-microenvironment-responsive biodegradable nano-platform for combination therapy favoring antitumor immune responses , 2017, Nature Communications.

[34]  Rutong Yu,et al.  Development of a hypoxia-triggered and hypoxic radiosensitized liposome as a doxorubicin carrier to promote synergetic chemo-/radio-therapy for glioma. , 2017, Biomaterials.

[35]  W. Sui,et al.  Non-enzymatic electrochemical biosensor based on Pt NPs/RGO-CS-Fc nano-hybrids for the detection of hydrogen peroxide in living cells. , 2016, Biosensors & bioelectronics.

[36]  W. Tan,et al.  A Smart Photosensitizer-Manganese Dioxide Nanosystem for Enhanced Photodynamic Therapy by Reducing Glutathione Levels in Cancer Cells. , 2016, Angewandte Chemie.

[37]  Zhengze Yu,et al.  A Near-Infrared Triggered Nanophotosensitizer Inducing Domino Effect on Mitochondrial Reactive Oxygen Species Burst for Cancer Therapy. , 2015, ACS nano.

[38]  T. Mak,et al.  Modulation of oxidative stress as an anticancer strategy , 2013, Nature Reviews Drug Discovery.

[39]  P. Storz.  Oxidative Stress in Cancer , 2013 .

[40]  Nicola J. Curtin,et al.  DNA repair dysregulation from cancer driver to therapeutic target , 2012, Nature Reviews Cancer.