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Pyroptosis therapy targeting TNBC

ABSTRACT: Biomimetic nanococrystals are prepared using the preferred combination of mitoxantrone and gambogic acid for rational drug delivery. The unique mechanism of obtained nanococrystals regulating pyroptosis genes through ribosomal stress is revealed by TMT-proteomics of 4T1 cells.

INSTRUMENT(S): Orbitrap Fusion Lumos

ORGANISM(S): Mus Musculus (mouse)

TISSUE(S): Malignant Cell, Cell Culture

DISEASE(S): Breast Cancer

SUBMITTER: Boshu Ouyang

LAB HEAD: Zhiqing Pang

PROVIDER: PXD053939 | Pride | 2024-07-27

REPOSITORIES: Pride

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Project description:A Cytotoxic T lymphocyte-inspired system capable of using ultralow-dose chemical drugs to manipulate cell death is needed to investigate the antitumour immunotherapy. Recent studies revealed pyroptosis, a proinflammatory type of cell death, could promote antitumour immune function. However, high-dose chemotherapy led to cytokine release syndrome by pyroptosis. Therefore, pyroptosis- inducing ultralow-dose chemotherapy was potential in preclinical and clinical research, but its efficacy, safety and the antitumour immune responses were not clear. Here, we established a near-infrared light controllable killing system (BIK system) by which ultralow-dose doxorubicin could be spatiotemporally transported to immunosuppressive tumour cells and mediate efficient pyroptosis. Compared with using DOX directly, the BIK system reduced total drug consumption to less than one- thirtieth the common dose in vitro. MPI imaging and fluorescence imaging showed our BIK system exhibited good tumour targeting and tumour penetration. We applied this system for pyroptosis-induced antitumor therapies, and the results showed that less than 43 µg kg-1 DOX was sufficient for GSDME-positive tumour regression with negligible injuries to major organs. Notably, the gasdermin-deficient 4T1 tumours could be controlled by combining BIK system with decitabine treatment. The antitumour immune function were proven to correlate with the impressive efficacy of pyroptosis-inducing ultralow-dose chemotherapy, and the concomitant immune memory prevented metastasis, but high-dose DOX led to poor T cells infiltration which caused immunosuppression and lung metastasis. Owing to the robust antitumour immune function induced by BIK system, advanced-stage bulky tumours could be controlled or shrunken by synergizing with anti-PD-1 therapy. This study provided new insights into the design of nanoassisted systems for activating the antitumour immune function by microstimulation; our application of the BIK system suggested that ultralow-dose chemotherapy was sufficient for inducing a robust pyroptosis-mediated antitumour immune function

			Action	DRS
	Lumos_TMT_QPN020_F1.raw	Raw
	Lumos_TMT_QPN020_F10.raw	Raw
	Lumos_TMT_QPN020_F2.raw	Raw
	Lumos_TMT_QPN020_F3.raw	Raw
	Lumos_TMT_QPN020_F4.raw	Raw

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Pyroptosis therapy targeting TNBC

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