Abstract
Nanoparticles offer a promising platform for drug delivery due to their long circulation time, enhanced solubility, low toxicity and excellent targeting of lesions. Herein, we report an AIEgen-Poly (I:C) composite nanoparticle (P@AP) for dual-modality tumor photodynamic-immunotherapy. Its specific size and capacity for partial degradation under acidic conditions determine its enhanced EPR effect. By complexing with the immunoadjuvant Poly(I:C), the immune silencing mechanism induced by apoptosis can be overcome and ICD is evoked efficiently at the cellular level. In the process of antigen presentation, P@AP, as an exogenous antigen, on the one hand, strengthens the expression of antigen presentation signal molecule MHC II and activates CD4+ T cells, on the other hand, enhancing pAPC infiltration by the increase of endogenous antigens represented by damage-associated molecular patterns while expressing MHC I via antigenic cross-presentation remarkably induces activation of CD8+ T cells, directly enhancing the killing of target cells. Massive immune arousal results in sustained tissue-resident memory T-cell residency in melanoma and reduces expression of CD4+ subsets of Treg cells, thereby prolonging the survival of subcutaneous melanoma mice and ridding of the poor prognosis of malignant melanoma stemming from its auto-immunosuppressive properties.
Published Version
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