Dual drugs decorated bacteria irradiate deep hypoxic tumor and arouse strong immune responses

Chen, Wenfei; He, Chun‐Ting; Qiao, Nan; Guo, Zhaofei; Hu, Shilong; Song, Yuanshuai; Wang, Hairui; Zhang, Zhirong; Ke, Bowen; Sun, Xun

doi:10.1016/j.biomaterials.2022.121582

Cited by 41 publications

(25 citation statements)

References 60 publications

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“…Previous studies have indicated that JQ-1 promotes antitumor immunity by suppressing the expression of PD-L1 on the cytomembrane at the transcriptional level. 51,52 Besides the cytomembrane, we found that CJ 2 can also decrease PD-L1 protein expression in the cytoplasm, suggesting that a different pathway may be involved in CJ 2 regulating the PD-L1 expression. To further investigate this conjecture, we first assessed the PD-L1 expression levels treated with a protein synthesis inhibitor cycloheximide (CHX).…”

Section: ■ Introductionmentioning

confidence: 87%

CJ₂: A Novel Potent Platinum(IV) Prodrug Enhances Chemo-Immunotherapy by Facilitating PD-L1 Degradation in the Cytoplasm and Cytomembrane

Fan

Deng

et al. 2023

J. Med. Chem.

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Platinum drugs as primary chemotherapy drugs have been applied to various cancer patients. However, their therapeutic applicability is limited due to the adverse effects and immunosuppression. To minimize the side effects and boost the immune response, we designed and synthesized platinum(IV) prodrugs that introduced BRD4 inhibitor JQ-1. Among them, CJ 2 had the most potent therapeutic activity and less toxicity. With the introduction of ligand JQ-1, CJ 2 -reduced PD-L1 protein was found in the cytoplasm and cytomembrane for the first time. By interfering with the PD-L1 synthesis, CJ 2 could arouse the immune system and promote CD8+ T cell infiltration. Meanwhile, CJ 2 could accelerate PD-L1 degradation in the cytoplasm to block DNA damage repair. In vivo, CJ 2 markedly suppressed tumor growth by reversing the immunosuppression microenvironment and enhancing DNA damage. These findings provide an effective approach to improve the selectivity and activity of the platinum drugs with elevated immune response.

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Section: ■ Introductionmentioning

confidence: 87%

CJ₂: A Novel Potent Platinum(IV) Prodrug Enhances Chemo-Immunotherapy by Facilitating PD-L1 Degradation in the Cytoplasm and Cytomembrane

Fan

Deng

et al. 2023

J. Med. Chem.

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“…coli to achieve enhanced antitumor photo/immunotherapy via multiple immunostimulatory pathways . Chen et al also proposed a bacterial carrier, which was coloaded PTT cyanine dye and JQ-1 carboxylic acid via chemical conjugations for a synergistic antitumor effect of PTT and immunotherapy . Sun et al conjugated Dox onto the surface of glucose dehydrogenase (GDH) overexpressed E.…”

Section: Immune Cell-based Drug Carriers For Cancer Immunotherapymentioning

confidence: 99%

Harnessing Engineered Immune Cells and Bacteria as Drug Carriers for Cancer Immunotherapy

et al. 2023

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Immunotherapy continues to be in the spotlight of oncology therapy research in the past few years and has been proven to be a promising option to modulate one's innate and adaptive immune systems for cancer treatment. However, the poor delivery efficiency of immune agents, potential off-target toxicity, and nonimmunogenic tumors significantly limit its effectiveness and extensive application. Recently, emerging biomaterial-based drug carriers, including but not limited to immune cells and bacteria, are expected to be potential candidates to break the dilemma of immunotherapy, with their excellent natures of intrinsic tumor tropism and immunomodulatory activity. More than that, the tiny vesicles and physiological components derived from them have similar functions with their source cells due to the inheritance of various surface signal molecules and proteins. Herein, we presented representative examples about the latest advances of biomaterial-based delivery systems employed in cancer immunotherapy, including immune cells, bacteria, and their derivatives. Simultaneously, opportunities and challenges of immune cells and bacteria-based carriers are discussed to provide reference for their future application in cancer immunotherapy.

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“…75 In addition to light sources and photosensitizers, oxygen is an indispensable part of the PDT process. However, hypoxic conditions, such as in tumor site 76 and bacterial infection microenvironments, 77 severely inhibit the efficacy of PDT. In order to alleviate the hypoxia, a number of oxygen-producing materials (nanozymes, hydrogel, microalgae, etc. )…”

Section: Design and Biomedical Applications Of Single Exogenous Stimu...mentioning

confidence: 99%

Research progress of stimuli-responsive ZnO-based nanomaterials in biomedical applications

Weng

Gao

et al. 2023

Biomater. Sci.

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Dual drugs decorated bacteria irradiate deep hypoxic tumor and arouse strong immune responses

Cited by 41 publications

References 60 publications

CJ₂: A Novel Potent Platinum(IV) Prodrug Enhances Chemo-Immunotherapy by Facilitating PD-L1 Degradation in the Cytoplasm and Cytomembrane

CJ₂: A Novel Potent Platinum(IV) Prodrug Enhances Chemo-Immunotherapy by Facilitating PD-L1 Degradation in the Cytoplasm and Cytomembrane

Harnessing Engineered Immune Cells and Bacteria as Drug Carriers for Cancer Immunotherapy

Research progress of stimuli-responsive ZnO-based nanomaterials in biomedical applications

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Dual drugs decorated bacteria irradiate deep hypoxic tumor and arouse strong immune responses

Cited by 41 publications

References 60 publications

CJ2: A Novel Potent Platinum(IV) Prodrug Enhances Chemo-Immunotherapy by Facilitating PD-L1 Degradation in the Cytoplasm and Cytomembrane

CJ2: A Novel Potent Platinum(IV) Prodrug Enhances Chemo-Immunotherapy by Facilitating PD-L1 Degradation in the Cytoplasm and Cytomembrane

Harnessing Engineered Immune Cells and Bacteria as Drug Carriers for Cancer Immunotherapy

Research progress of stimuli-responsive ZnO-based nanomaterials in biomedical applications

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Product

Resources

About

CJ₂: A Novel Potent Platinum(IV) Prodrug Enhances Chemo-Immunotherapy by Facilitating PD-L1 Degradation in the Cytoplasm and Cytomembrane

CJ₂: A Novel Potent Platinum(IV) Prodrug Enhances Chemo-Immunotherapy by Facilitating PD-L1 Degradation in the Cytoplasm and Cytomembrane