A Cancer Nanovaccine Based on an FeAl-Layered Double Hydroxide Framework for Reactive Oxygen Species-Augmented Metalloimmunotherapy

Abstract

The complexity and heterogeneity of individual tumors have hindered the efficacy of existing therapeutic cancer vaccines, sparking intensive interest in the development of more effective in situ vaccines. Herein, we introduce a cancer nanovaccine for reactive oxygen species-augmented metalloimmunotherapy in which FeAl-layered double hydroxide (LDH) is used as a delivery vehicle with dihydroartemisinin (DHA) as cargo. The LDH framework is acid-labile and can be degraded in the tumor microenvironment, releasing iron ions, aluminum ions, and DHA. The iron ions contribute to aggravated intratumoral oxidative stress injury by the synergistic Fenton reaction and DHA activation, causing apoptosis, ferroptosis, and immunogenic cell death in cancer cells. The subsequently released tumor-associated antigens with the aluminum adjuvant form a cancer nanovaccine to generate robust and long-term immune responses against cancer recurrence and metastasis. Moreover, Fe ion-enabled T 1 -weighted magnetic resonance imaging can facilitate real-time tumor therapy monitoring. This cancer-nanovaccine-mediated metalloimmunotherapy strategy has the potential for revolutionizing the precision immunotherapy landscape.

Photoimmunotherapy-Induced Pyroptosis Remodels the Microenvironment to Enhance Cancer Immunotherapy

“…It is typically accompanied by the release of numerous inflammatory molecules and cellular contents such as lactate dehydrogenase (LDH). The degradation of LDH in the tumor microenvironment can contribute to cancer cell apoptosis and immunogenic cell death by exacerbating oxidative stress within the tumor . As shown in Figure c, the PDI+Light group significantly stimulated the release of LDH, resulting in much higher levels of LDH in the cellular supernatants compared to the control groups.…”

A “Ferroptosis-Amplifier” Hydrogel for Eliminating Refractory Cancer Stem Cells Post-lumpectomy

“…This unique iron metabolism is also linked to stemness maintenance. , Previous studies have revealed that the iron addiction of CSCs also makes them vulnerable to ferroptosis inducers, which makes ferroptosis a potential process to combat CSCs. Arising types of iron-based ferroptosis inducers have been developed to trigger an intracellular Fenton reaction, including ion oxides, LDH, or FeP . Several strategies having been proposed to promote the limited Fenton catalytic efficiency, such as introducing reductive components (EGCG) to reduce Fe 3+ to Fe 2+ .…”