A protein-based cGAS-STING nanoagonist enhances T cell-mediated anti-tumor immune responses.

ABSTRACT: cGAS-STING pathway is a key DNA-sensing machinery and emerges as a promising target to overcome the immunoresistance of solid tumors. Here we describe a bovine serum albumin (BSA)/ferritin-based nanoagonist incorporating manganese (II) ions and β-lapachone, which cooperatively activates cGAS-STING signaling in dendritic cells (DCs) to elicit robust adaptive antitumor immunity. Mn²⁺-anchored mannose-modified BSAs and β-lapachone-loaded ferritins are crosslinked to afford bioresponsive protein nanoassemblies, which dissociate into monodispersive protein units in acidic perivascular tumor microenvironment (TME), thus enabling enhanced tumor penetration and spatiotemporally controlled Mn²⁺ and β-lapachone delivery to DCs and tumor cells, respectively. β-lapachone causes i

SUBMITTER: Wang X 

PROVIDER: S-EPMC9515186 | biostudies-literature | 2022 Sep

REPOSITORIES: biostudies-literature