A “CPApoptosis” nano-actuator switches immune-off solid tumors to immune-on for fueling T-cell- based immunotherapy DOI Creative Commons
Ying Luo, Yi Wang, Bo Liu

и другие.

Theranostics, Год журнала: 2025, Номер 15(9), С. 3797 - 3820

Опубликована: Март 3, 2025

Background: Most anticancer agents induce tumor apoptosis, but they often lack immunogenicity and display limited success when combined with mainstream immunotherapies, thus killing cancer cells through multiple cell death modalities as well switching immune-off tumors to immune-on is a strategy great promise. To this end, we developed CPApoptosis (cuproptosis, pyroptosis, apoptosis) nano-actuator for immunologically cold solid tumors. Methods: In study, elesclomol (ES), mitochondrial targeting copper transporter, was encapsulated within bacterial outer membrane vesicles (OMVs). These OMVs were then surface-modified via metal-phenolic self-assembly using Cu2+ tannic acid (TA). Results: The ES released from the in pH-dependent manner. OMV activated non-canonical pyroptotic pathway, leading rupture. on one hand transported mitochondria cuproptosis facilitated by ES, other hand, reduced into Cu+ TA, which catalyzed ROS production oxidative apoptosis. Simultaneously, TA degraded glutathione (GSH), sensitizing cuproptosis. multifactorial mechanisms led release of immunogenic factors lysed cells, stimulating dendritic maturation recruiting cytotoxic T cells. This immune response further amplified αPD-L1 antibody treatment. Conclusion: represents promising approach enhance current therapies, inducing both robust response, potential long-lasting protective effects.

Язык: Английский

A “CPApoptosis” nano-actuator switches immune-off solid tumors to immune-on for fueling T-cell- based immunotherapy DOI Creative Commons
Ying Luo, Yi Wang, Bo Liu

и другие.

Theranostics, Год журнала: 2025, Номер 15(9), С. 3797 - 3820

Опубликована: Март 3, 2025

Background: Most anticancer agents induce tumor apoptosis, but they often lack immunogenicity and display limited success when combined with mainstream immunotherapies, thus killing cancer cells through multiple cell death modalities as well switching immune-off tumors to immune-on is a strategy great promise. To this end, we developed CPApoptosis (cuproptosis, pyroptosis, apoptosis) nano-actuator for immunologically cold solid tumors. Methods: In study, elesclomol (ES), mitochondrial targeting copper transporter, was encapsulated within bacterial outer membrane vesicles (OMVs). These OMVs were then surface-modified via metal-phenolic self-assembly using Cu2+ tannic acid (TA). Results: The ES released from the in pH-dependent manner. OMV activated non-canonical pyroptotic pathway, leading rupture. on one hand transported mitochondria cuproptosis facilitated by ES, other hand, reduced into Cu+ TA, which catalyzed ROS production oxidative apoptosis. Simultaneously, TA degraded glutathione (GSH), sensitizing cuproptosis. multifactorial mechanisms led release of immunogenic factors lysed cells, stimulating dendritic maturation recruiting cytotoxic T cells. This immune response further amplified αPD-L1 antibody treatment. Conclusion: represents promising approach enhance current therapies, inducing both robust response, potential long-lasting protective effects.

Язык: Английский

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