A bioorthogonal-catalytic artificial antigen-presenting cell for chemo- and immuno-therapy

Abstract

Bioorthogonal prodrug activation has emerged as a promising strategy in tumor therapy. However, its clinical translation is hindered by limited therapeutic efficacy due to the complexity of tumors and heterogeneity of individuals. Herein, an artificial antigen-presenting cell (aAPC)-based biomimetic bioorthogonal catalyst is developed by encapsulating transition metal catalysts (TMCs) within lipid nanoparticles cloaked with dendritic cell membranes (LNP-Fe@dcM). By imitating key immune cell functions, LNP-Fe@dcM mediates a dual-mode antitumor response via catalytic prodrug activation and immunomodulation. Particularly, localized activation of a doxorubicin prodrug kills tumor cells and induces immunogenic cell death (ICD), thereby releasing tumor-associated antigens and priming personalized antitumor immunity. Concurrently, dendritic cell membrane-derived ligand-receptor interactions facilitate T cell activation and proliferation. This synergistic strategy enables efficient antigen presentation and robust immune activation. The presented approach offers a versatile paradigm for engineering catalytic aAPCs toward bioorthogonal cancer immunotherapy.