Eliciting Immunogenic Cell Death via a Unitized Nanoinducer.

ABSTRACT

Utilizing chemotherapeutics to induce immunogenic cell death (ICD) is a promising strategy to sensitize tumor cells and induce anticancer immunity. However, the application of traditional ICD inducers, such as chemodrugs, is largely hindered by their low tumor selectivity and severe side effects. Here, a new unitized ICD nanoinducer with high potency and cancer cell specificity is reported to achieve effective cancer immunotherapy. This nanoinducer is composed of disulfide-bond-incorporated organosilica nanoparticles, curcumin (CUR), and iron oxide nanoparticles, which can deplete intracellular glutathione, produce hydroxyl radicals, and induce cancer-cell-specific Ca2+ depletion as well as thioredoxin reductase inhibition. While the components are unable to induce ICD individually, their complementary pharmaceutical activities significantly elevate intracellular oxidative stress and endoplasmic reticulum stress in parallel. Consequently, ICD and systemic antitumor immunity can be elicited. Compared to the conventional ICD inducer doxorubicin, the unitized nanoinducer exhibits significantly improved ICD-inducing activity and cancer cell selectivity.