ACS Applied Materials & Interfaces
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2021
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IF 9.229
Yu Sun,Jing Cao,Xue Wang,Cong Zhang,Jiali Luo,Yiqing Zeng,Chao Zhang,Qunying Li,Ying Zhang,Wen Xu,Tao Zhang,Pintong Huang
The efficacy of sonodynamic therapy (SDT) is largely dependent upon oxygen availability to generate deleterious reactive oxygen species, and as such, hypoxic microenvironments greatly constrain the efficacy of SDT. Development of free radical generators that are not dependent on oxygen and related combination treatment strategies thus have the potential to enhance the antitumor potential of SDT. Combined treatment strategies are expected to improve the efficacy of sonodynamic antitumor therapy. As metal–organic framework (MOF) platforms are highly amenable to integration with other therapeutic approaches, we herein report the development of tumor microenvironment (TME)-responsive nanoparticles constructed by embedding the azo initiator 2,2′-azobis[2-(2-imidazolin-2-yl)propane]dihydrochloride (AIPH) into hypoxia-triggered copper metal–organic framework (Cu-MOF) nanovectors to achieve synergistic sono-chemodynamic therapy in an orthotopic murine pancreatic carcinoma model system. When exposed to hypoxic conditions within the TME, this Cu-MOF structure underwent degradation, leading to the release of Cu2+ and AIPH. Cu2+ was then able to deplete local glutathione stores, resulting in the reduction of Cu2+ to Cu+, which then reacts with endogenous H2O2 in a Fenton-like reaction to yield cytotoxic hydroxyl radicals (•OH) for chemodynamic therapy. When exposed to ultrasound irradiation, AIPH further degraded in an oxygen-independent manner to yield nitrogen bubbles and alkyl radicals, the former of which enhanced the ability of these nanoparticles to penetrate deeply into the tumor. The resultant radicals induced substantial DNA damage and apoptotic cell death within target tumors under different levels of oxygen availability. As such, this hypoxic TME-responsive synergistic sono-chemodynamic approach offers an ideal means of achieving oxygen-independent free radical generation and enhanced treatment efficacy.
研究领域:
肿瘤学
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纳米技术
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癌症治疗策略
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生物医学工程
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Translational Oncology
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2023
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IF 5
Jiale Cai,Guiping Hu,Lihua Hu,Junge Chen,Dan Chen,Dan Liu,Xiaolei Wang,Boxian Hu,Cheng Li
Introduction Sonodynamic therapy (SDT) has potential clinical applications for cancer therapy, and is yet restricted by complex tumor microenvironmental (TME) factors. Thus, the research problem of TME modulation as well as efficient tumor treatment still needs to be clarified. Method In this study, a calcium carbonate (CaCO 3 ) nanoplatform was designed for ultrasound (US) and TME response-triggered, which encapsulated Ag 2 S and loaded with l -Arg, and further wrapped with RBC/Platelet membrane, named as QD@Ca/M L-Arg . Results Non-invasive US-triggered SDT by Ag 2 S and acidic environment-responsive drug release were achieved. In vitro experiments validated the efficacy of SDT, Ca-ion interference and nitric oxide (NO) gas therapy as combined therapy for cancer treatment. By means of RNA sequencing, the cancer therapeutic mechanism of SDT in redox-related pathways was elucidated. The immunosuppressive TME was simulated with a M2-macrophage/cancer cell co-culture system to confirm the immune activating effect of immunogenic cell death (ICD). Conclusion Accordingly, the potential of QD@Ca/M L- Arg- was demonstrated for in vitro TME modulation, cancer therapeutic efficacy and clinical translation.
研究领域:
癌症治疗
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纳米技术
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生物医学工程
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分子生物学
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免疫学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
CHEMICAL ENGINEERING JOURNAL
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2023
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IF 15.1
Yilin Yang,Ning Wang,Zhihua Wang,Mingda Han,Fei Yan,Zhan Shi,Shouhua Feng
Sonodynamic therapy (SDT) has emerged as a promising strategy for treating tumors owing to its non-invasiveness and high tissue-penetrating depth. Improving the efficiency of electron-hole separation of sonosensitizers and alleviation of the hypoxic tumor microenvironment remain major challenges. Metal-organic frameworks (MOFs) have greatly potential in SDT application, however, exploring new sonosensitizers with high reactive oxygen species (ROS) generation and improving the efficacy through a synergistic effect in combination with other therapeutic modalities remain major challenges. Furthermore, the immunosuppressive tumor microenvironment (TME) is characterized by hypoxia, which limit the efficacy of O 2 -dependent cancer treatments including SDT and immunotherapy. Herein, we fabricated a defect-rich titanium-based MOFs using propionic acid-mediated self-templated hierarchical etching. Reductive platinum nanoparticles were embedded onto the surface of MOFs to enhance the spatial separation of electron-hole pairs and improve the quantum yield of ultrasound-generated singlet oxygen ( 1 O 2 ). Finally, perfluorobromooctane was encapsulated in the MOFs to function as an oxygen carrier to develop an oxygen self-feeding nanosensitizer. In vitro and in vivo assays demonstrated that this nanoplatform could produce high levels of 1 O 2 under ultrasound irradiation, which led to enhanced SDT. Moreover, this nanoplatform also relieved the immunosuppressive TME by overcoming hypoxia and enhancing immunogenic cell death to promote the infiltration of tumor-specific cytotoxic T cells into the immunologically “cold” tumor. Therefore, combination of nanoplatform-mediated SDT with anti-PDL1 antibodies effectively inhibited the primary tumors, as well as the metastatic tumors. This study provides an insightful strategy for improving SDT and broadens the application of MOF-based sonosensitizers for sono-immunotherapy.
研究领域:
癌症治疗
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纳米技术
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生物医学工程
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材料科学
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免疫疗法
✓ 已验证
产品关联
DOI
高影响因子
CHEMICAL ENGINEERING JOURNAL
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2024
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IF 13.3
Haoyu Chen,Xiaoying Kong,Jiahui Yan,Tianyi Wang,Yaqian Lv,Fenglang Zhang,Danping Liu,Yingshan Qu,Jun Fu,Wei Han,Jinsheng Shi
Combined dynamic tumor therapy of photodynamic therapy (PDT), sonodynamic therapy (SDT) and microwave dynamic therapy (MDT) can overcome the limitations of single reactive oxygen species (ROS)-based therapy (including limited tissue penetration depth and low ROS production). However, changes in the tumor microenvironment caused by ROS amplification and oxygen depletion induce severe immunosuppression at the tumor site, indicating effective immunosensitization of the tumors are urgently needed. Here, melanin-hematoporphyrin-chloroquine R837-hyaluronic acid (MHRH) nanoplatform that can simultaneously respond to 980 nm laser /1064 nm laser/ultrasonic/microwave was prepared for PDT/SDT/MDT, achieving outbreak of ROS in deep tumor. More importantly, the photothermal ablation and the participation of chloroquine R837 of MHRH NPs reversed the immunosuppression caused by oxygen depletion after ROS outbreak by promoting DCs maturation and secretion of macrophage exosomes. In summary, the natural MHRH nano-platform supplies an obvious anti-tumor “butterfly effect” through ROS outbreak, thermal ablation and significant immunosuppressive reversal, which provides a new and promising combined strategy of ROS-dynamic therapy and immune agonists in deep tumor tissues.
研究领域:
癌症治疗
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纳米技术
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免疫治疗
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生物医学工程
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肿瘤学
✓ 已验证
产品关联
DOI
高影响因子
ACS Nano
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2025
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IF 16
Yilin Yang,Ning Wang,Zhihua Wang,Fei Yan,Zhan Shi,Shouhua Feng
Despite the potential of sonodynamic therapy (SDT) in treating malignant tumors, the lack of effective sonosensitizers has limited its clinical implementation. In this study, we explored the relationship between the heteroatom doping concentration in metal–organic frameworks and interface formation after pyrolysis by regulating the addition of manganese sources and successfully derived Z-scheme heterojunctions MnxOy/(A/R)TiO2 (MTO) in situ from MIL-125-NH2 (Ti/Mn). The electron transfer pathway introduced by interfacial contact promoted carrier separation and greatly preserved the effective redox components, significantly influencing the performance of reactive oxygen species generation. Upon reaching the tumor sites, MTO effectively depleted glutathione to alleviate the suppressive tumor environment, and the heterojunctions and MnxOy in MTO facilitated SDT and synergistic chemodynamic therapy (CDT), respectively, leading to enhanced immunogenic cell death (ICD). Furthermore, Mn2+ uptake by dendritic cells (DCs) and the tumor-associated antigens released due to ICD activated the stimulator of interferon genes pathway, which elicited a robust tumor-specific immune response by driving the maturation of DCs and the activation of T cells. In addition, the activated T cells secreted high levels of interferon-γ to enhance Mn3+/Mn2+-mediated ferroptosis in metastatic tumor cells. The combination of MTO-mediated synergistic therapy and PD-L1 checkpoint blockade exhibited vaccine-like functions, inducing stronger systemic immunity and durable immune memory to inhibit tumor progression, metastasis, and recurrence. To summarize, we synthesized a self-enhancing nanoplatform for synergistic SDT/CDT/immunotherapy using multifunctional MOF-derived Z-scheme heterojunctions. This study provides an experimental basis for amplifying the potential of sonosensitizers while optimizing SDT-mediated systemic immunity while avoiding interference caused by additional adjuvants.
研究领域:
癌症治疗
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纳米技术
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材料科学
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免疫学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
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