Reinforcing the Induction of Immunogenic Cell Death Via Artificial Engineered Cascade Bioreactor-Enhanced...

Traditional chemo-immunotherapy can elicit T cell immune response by inducing immunogenic cell death (ICD), however, insufficient ICD limits the lasting antitumor immunotherapeutic efficacy. Herein, tadpole-ovoid manganese-doped hollow mesoporous silica coated gold nanoparticles (Au@HMnMSNs) as biodegradable catalytic cascade nanoreactors are constructed to generate intratumoral high-toxic hydroxyl radicals combined with DOX and Aspirin (ASA) for enhancing the induction of ICD and maturation of dendritic cells (DCs). The released Mn²⁺ can catalyze endogenous H₂ O₂ to hydroxyl radicals, while internal gold nanoparticles mimetic glucose oxidase (GOx) converted glucose into H₂ O₂ to accelerate the generation of hydroxyl radicals. On the other hand, tadpole oval-structured Au@HMnMSNs can avoid the inactivation of gold nanoparticles due to strong protein adsorption. The introduction of ASA is to recruit DCs and cytotoxic T lymphocytes (CTLs) to tumor sites and restrain the intratumoral infiltration of immunosuppressive cells by decreasing the expression of prostaglandin E2 (PGE₂ ). Accordingly, this work presents a novel insight to introduce GOx-like catalytic cascade ICD nano-inducer into antitumor immunotherapy for synergistic tumor therapy.