Virus-mimicking nanoparticle potentiates in-situ cancer vaccines by reversing intratumoral DCs via stimulating cytosolic nucleic acid sensors.

The major challenge for in-situ cancer vaccines is to activate the dendritic cells (DCs) within the immunosuppressive tumor to initiate tumor-specific immune responses. By contrast, oncolytic viruses can always activate intratumoral DCs to initiate virus-specific immunity to eliminate viruses which will in turn reduce the anti-tumor effect of these viruses. To bridge the two approaches, we developed virus-mimicking nanoparticle (V-mimic) through self-assembly of artificial cyclic gadolinium-based GAMP (c·Gd·GAMP, a STING agonist), double-stranded RNA analog (Poly I:C), and indocyanine green (ICG).

Multifunctional nanoparticles potentiate in-situ tumor vaccines via reversing insufficient Photothermal therapy by disrupting tumor vasculature.

Photothermal therapy can trigger immunogenic cell death and release personalized in-situ tumor vaccine, activating immune responses to eliminate systemic tumors beyond the irradiated zone. However, the immune response of the in-situ tumor vaccines is often undermined by the residual tumor cells and their induced immunosuppressive tumor microenvironment (TME), which is attributed to insufficient photothermal effects stemming from the limited accumulation of photosensitizers. To overcome these limitations, we developed multi-functional nanoparticles (VI@Gd-NPs) that integrate a tumor vasculature-specific disrupting agent (Vadimezan, Phase III clinical drug), a photosensitizer (Indocyanine Green, ICG), and a magnetic resonance imaging contrast agent (Gadolinium, Gd) through chemical self-assembly.