JOURNAL OF COLLOID AND INTERFACE SCIENCE
·
2022
·
IF 9.965
Pengfei Yang,Yi Chang,Jie Zhang,Fangli Gao,Xinhe Liu,Qingcong Wei,Xiaoming Ma,Yuming Guo
Photodynamic therapy (PDT) is proved to be a promising modality for clinical cancer treatment. However, it also suffers from a key obstacle in association with its oxygen-dependent nature which greatly limits its effective application against hypoxic tumors. Herein, on the basis of the unique property of calcium peroxide (CaO 2 ), we propose an O 2 -self-supply strategy for the promotion of PDT by combining the in situ O 2 -generation characteristic of calcium peroxide with the photosensitive nature of porphyrin . A shell of ZIF-8 was synthesized surround the CaO 2 core to prevent the CaO 2 from premature decomposition and increased the loading of THPP efficiently. Depending on the in situ self-supply of O 2 , the photosensitizer was able to exhibit an enhanced PDT effect that significantly inhibit the growth of tumor. Moreover, the enrichment of free calcium ions derived from the decomposition of CaO 2 under acidic tumor microenvironment also shows the unique ion-interference effect and contributes to the obvious inhibition against tumor growth. This work presents a synergistic strategy for the construction of a photodynamic promotion/ion-interference combined nano-platform which can also serve as an inspiration for the future design of effective nanocomposites in tumor treatment.
研究领域:
癌症治疗
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纳米医学
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生物医学工程
·
化疗
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Acta Biomaterialia
·
2024
·
IF 9.4
Cong Tang,Kairui Liu,Xiaoning Gao,Hanmeixuan Kang,Weijie Xie,Jin Chang,Linling Yin,Jun Kang
Cuproptosis is an emerging form of programmed cell death and shows enormous prospect in cancer treatment. Excessive generation of reactive oxygen species (ROS), metal ion accumulation, and the tricarboxylic acid (TCA) cycle collapse are pivotal elements in the triggering of cell death via mitochondrial pathways. Herein, a cascade nanoreactor CaCuZC has been constructed by incorporating nanosonosensitizer IR780 carbon dots (IR780 CD) and calcium peroxide (CaO 2 ) into metal-organic frameworks (MOF) for synergistic cuproptosis–ferroptosis and Ca 2+ overload mediated immunotherapy. Within tumor cells, CaCuZC dissociates into CaO 2 , Cu 2+ and sonosensitizer IR780 CD. The decomposition of CaO 2 could generate H 2 O 2 to strengthen the Cu 2+ -based chemodynamic therapy and Ca 2+ overload induces amplified intracellular oxidative stress, thus leading to mitochondrial dysfunction. As a result, the combination of Cu 2+ and Ca 2+ overload together induce cascade mitochondrial damage. Moreover, the sonosensitizer IR780 CD generates ROS under ultrasound irradiation to amplify intracellular oxidative stress. In addition, the overloaded Cu 2+ released from CaCuZC leads to the aggregation of lipoylated protein dihydrolipoamide S-acetyltransferase, thus resulting in cuproptosis. Furthermore, ferroptosis could been concomitantly induced by CaCuZC with intracellular glutathione (GSH) consumption and lipid peroxidation (LPO) accumulation. The cuproptosis–ferroptosis and Ca 2+ overload-enhanced synergistic therapy also activates robust immunogenic cell death. CaCuZC enhances the infiltration and activation of tumor-specific cytotoxic T cells to transform a “cold” tumor into a “hot” tumor, activating the anti-tumor immune response. This study provides a cascade of mitochondrial damage strategy for triggering cuproptosis–ferroptosis and Ca 2+ overload-enhanced immunotherapy and achieving improved therapeutic effects. Statement of significance To improve the efficacy of tumor immunotherapy, a cascade nanoreactor CaCuZC was successfully constructed based on a self-assembly strategy for cuproptosis–ferroptosis and Ca 2+ overload mediated immunotherapy. Upon decomposition within the acidic and GSH-overexpressing tumor microenvironment, CaCuZC released CaO 2 and Cu 2+ and sonosensitizer IR780 CD. The CaO 2 further produced H 2 O 2 /O 2 and Ca 2+ in a weakly acidic environment to strengthen the Cu 2+ -based CDT and IR780 CD-mediated SDT, respectively. The overload copper ions not only led to cuproptosis, but also efficiently induced ferroptosis. The cuproptosis–ferroptosis and Ca 2+ overload-enhanced synergistic therapy also activates robust immunogenic cell death. This study presents a cascade of mitochondrial damage strategy for cuproptosis–ferroptosis and Ca 2+ overload-enhanced immunotherapy.
研究领域:
癌症研究
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纳米技术
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治疗学
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免疫学
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生物化学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Advanced Healthcare Materials
·
2023
·Vol. 12
·期 12
·2202424
·
IF 10
Dongdong Guo,Xiaoyong Dai,Kewei Liu,Yuhong Liu,Jiamin Wu,Kun Wang,Shengwei Jiang,Fen Sun,Lijun Wang,Bing Guo,Dongye Yang,Laiqiang Huang
While calcium-overload-mediated therapy (COMT) is a promising but largely untapped therapeutic strategy, combinatory therapy greatly boosts treatment outcomes with integrated merits of different therapies. Herein, a BPQD@CaO 2 -PEG-GPC3Ab nanoplatform is formulated by integrating calcium peroxide (CaO 2 ) and black phosphorus quantum dot (BPQD, photosensitizer) with active-targeting glypican-3 antibody (GPC3Ab), for combinatory photodynamic therapy (PDT) and COMT in response to acidic pH and near-infrared (NIR) light, wherein CaO 2 serves as the reservoir of calcium ions (Ca 2+ ) and hydrogen peroxide (H 2 O 2 ). Navigated by GPC3Ab to tumor cells at acidic pH, the nanoparticle disassembles to CaO 2 and BPQD; CaO 2 produces COMT Ca 2+ and H 2 O 2 , while H 2 O 2 makes oxygen (O 2 ) to promote PDT; under NIR irradiation BPQD facilitates not only the conversion of O 2 to singlet oxygen ( 1 O 2 ) for PDT, but also moderate hyperthermia to accelerate NP dissociation to CaO 2 and BPQD, and conversions of CaO 2 to Ca 2+ and H 2 O 2 , and H 2 O 2 to O 2 , to enhance both COMT and PDT. After supplementary ionomycin treatment to induce intracellular Ca 2+ bursts, the multimodal therapeutics strikingly induce hepatocellular carcinoma apoptosis, likely through the activation of the calpains and caspases 12, 9, and 3, up-regulation of Bax and down-regulation of Bcl-2 proteins. This nanoplatform enables a mutually-amplifying and self-reinforcing synergistic therapy.
研究领域:
癌症治疗
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纳米技术
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光动力疗法
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钙信号
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药物递送系统
✓ 已验证
产品关联
DOI
PubMed
高影响因子
危险品化学品经营许可证（带存储）