Photothermal self-adjuvant porous microneedles for self-healing encapsulation and sustained release of antigens to improve adaptive immunity

Abstract

Effective vaccination hinges on overcoming persistent challenges in delivery site optimization, sustained antigen release, maintaining antigen integrity, and providing safe adjuvanticity. Here, we report a photothermal self-adjuvant porous microneedle (PSAPMN) patch as an all-in-one platform that comprehensively addresses these issues. Fabricated from polylactic-co-glycolic acid (PLGA) and polydopamine nanoparticles (PDA-NPs), the microneedles possess a unique interconnected porous architecture, enabling exceptionally mild, diffusion-based antigen loading. Upon brief near-infrared (NIR) irradiation, the photothermal effect of PDA-NPs not only accelerates pore self-healing for complete antigen encapsulation within 20 minutes but also creates a biodegradable depot for sustained intradermal release over 15 days. Crucially, the localized NIR-generated heat simultaneously serves as a potent physical adjuvant, promoting dendritic cell activation. In vivo, this integrated strategy elicits significantly more potent and durable antigen-specific immunity and immunological memory than conventional methods. This work presents a versatile platform for developing next-generation vaccines by synergistically solving multiple critical delivery challenges in a single device.