GSH depletion liposome adjuvant for augmenting the photothermal immunotherapy of breast cancer

Zhou, Zhanwei; Wu, Hui; Yang, Ruoxi; Xu, Alan; Zhang, Qingyan; Dong, Jingwen; Qian, Chenggen; Sun, Minjie

doi:10.1126/sciadv.abc4373

Cited by 152 publications

(97 citation statements)

References 42 publications

(50 reference statements)

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“…ROS enhances photothermal cancer therapy and induces ICD of tumor cells and promotes DC maturation and tumor antigen presentation. Therefore, this adjuvant therapy increased tumor infiltration of CD8+ T cells, elicited a strong abscopal effect, and significantly prevented tumor metastasis in a murine breast cancer model [ 256 ]. Similarly, thioredoxin has been recently evaluated to become a target to deal with TNBC, as this system is upregulated in TNBC cells to maintain homeostasis and is correlated with adverse survival outcomes.…”

Section: Immune System Immunotherapy and Antioxidants In Breast Cmentioning

confidence: 99%

Antioxidants for the Treatment of Breast Cancer: Are We There Yet?

et al. 2021

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Breast cancer is the most frequent cancer and the leading cause of cancer death in women. Oxidative stress and the generation of reactive oxygen species (ROS) have been related to cancer progression. Compared to their normal counterparts, tumor cells show higher ROS levels and tight regulation of REDOX homeostasis to maintain a low degree of oxidative stress. Traditionally antioxidants have been extensively investigated to counteract breast carcinogenesis and tumor progression as chemopreventive agents; however, there is growing evidence indicating their potential as adjuvants for the treatment of breast cancer. Aimed to elucidate whether antioxidants could be a reality in the management of breast cancer patients, this review focuses on the latest investigations regarding the ambivalent role of antioxidants in the development of breast cancer, with special attention to the results derived from clinical trials, as well as their potential use as plausible agents in combination therapy and their power to ameliorate the side effects attributed to standard therapeutics. Data retrieved herein suggest that antioxidants play an important role in breast cancer prevention and the improvement of therapeutic efficacy; nevertheless, appropriate patient stratification based on “redoxidomics” or tumor subtype is mandatory in order to define the dosage for future standardized and personalized treatments of patients.

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Section: Immune System Immunotherapy and Antioxidants In Breast Cmentioning

confidence: 99%

Antioxidants for the Treatment of Breast Cancer: Are We There Yet?

et al. 2021

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“…Immunotherapy is a novel strategy for tumor therapy that works via an activated immune system [ 1 – 3 ]. However, the tumor microenvironment is immunosuppressive, and conventional delivery of immune adjuvants and tumor-related antigens (TAAs) cannot effectively activate the tumor immune response [ 4 – 6 ]. There is low-infiltration of antigen-specific CD8 + cytotoxic T lymphocytes (CTLs) when the antigens or adjuvants are simply injected into the skin, thus leading to a limited therapeutic effects [ 7 ].…”

Section: Introductionmentioning

confidence: 99%

Functional nanovesicles displaying anti-PD-L1 antibodies for programmed photoimmunotherapy

et al. 2022

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Background Photoimmunotherapy is one of the most promising strategies in tumor immunotherapies, but targeted delivery of photosensitizers and adjuvants to tumors remains a major challenge. Here, as a proof of concept, we describe bone marrow mesenchymal stem cell-derived nanovesicles (NVs) displaying anti-PD-L1 antibodies (aPD-L1) that were genetically engineered for targeted drug delivery. Results The high affinity and specificity between aPD-L1 and tumor cells allow aPD-L1 NVs to selectively deliver photosensitizers to cancer tissues and exert potent directed photothermal ablation. The tumor immune microenvironment was programmed via ablation, and the model antigen ovalbumin (OVA) was designed to fuse with aPD-L1. The corresponding membrane vesicles were then extracted as an antigen–antibody integrator (AAI). AAI can work as a nanovaccine with the immune adjuvant R837 encapsulated. This in turn can directly stimulate dendritic cells (DCs) to boast the body's immune response to residual lesions. Conclusions aPD-L1 NV-based photoimmunotherapy significantly improves the efficacy of photothermal ablation and synergistically enhances subsequent immune activation. This study describes a promising strategy for developing ligand-targeted and personalized cancer photoimmunotherapy. Graphic Abstract

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“…The most common method for enhancing CDT performance is chemical depletion of intracellular GSH. Sulphydryl‐reactive agents, such as Cu(II), [ 8 ] SnFe 2 O 4 , [ 9 ] Bi 2 S 3 , [ 10 ] NiS 2 , [ 11 ] maleimide, [ 12 ] and p ‐quinone methide, [ 13 ] can react with biological thiols (e.g., GSH and cysteine) to weaken the cell antioxidant capacity and improve the effect of CDT. However, as the most abundant antioxidant found in living organisms, GSH in tumor cells is maintained at a high levels (about 5 × 10 −3 m ), [ 14 ] which places a high demand on the cellular uptake of exogenous agents.…”

Section: Introductionmentioning

confidence: 99%

A Ferrocene‐Functionalized Covalent Organic Framework for Enhancing Chemodynamic Therapy via Redox Dyshomeostasis

Zhou

Guan

et al. 2021

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Chemodynamic therapy (CDT), which induces cell death by decomposing high levels of H2O2 in tumor cells into highly toxic ·OH, is recognized as a promising antineoplastic approach. However, current CDT approaches are often restricted by the highly controlled and upregulated cellular antioxidant defense. To enhance ·OH‐induced cellular damage by CDT, a covalent organic framework (COF)‐based, ferrocene (Fc)‐ and glutathione peroxidase 4 (GPX4) inhibitor‐loaded nanodrug, RSL3@COF–Fc (2b), is fabricated. The obtained 2b not only promotes in situ Fenton‐like reactions to trigger ·OH production in cells, but also attenuates the repair mechanisms under oxidative stress via irreversible covalent GPX4 inhibition. As a result, these two approaches synergistically result in massive lipid peroxide accumulation, subsequent cell damage, and ultimately ferroptosis, while not being limited by intracellular glutathione. It is believed that this research provides a paradigm for enhancing reactive oxygen species‐mediated oncotherapy through redox dyshomeostasis and may provide new insights for developing COF‐based nanomedicine.

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GSH depletion liposome adjuvant for augmenting the photothermal immunotherapy of breast cancer

Cited by 152 publications

References 42 publications

Antioxidants for the Treatment of Breast Cancer: Are We There Yet?

Antioxidants for the Treatment of Breast Cancer: Are We There Yet?

Functional nanovesicles displaying anti-PD-L1 antibodies for programmed photoimmunotherapy

A Ferrocene‐Functionalized Covalent Organic Framework for Enhancing Chemodynamic Therapy via Redox Dyshomeostasis

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