Nanoparticle-integrated dissolving microneedles for the co-delivery of R848/aPD-1 to synergistically reverse the immunosuppressive microenvironment of breast cancer

Nowadays, effective immunotherapy against triple -negative breast cancer (TNBC) remains challenging due to the immunosuppressive tumor microenvironment. Immune checkpoint inhibitor is mostly employed to restore the activity of tumor -specific immune cells, which however brings little therapeutic outcome owing to the limited number of tumor -infiltrating CD8+ T cells and the inefficient delivery of immune drugs to the tumor tissue. Aiming to solve these problems, we herein constructed a tailor-made dissolving microneedle co -encapsulating the TLR7/8 agonist R848 and the immune checkpoint inhibitor aPD-1, termed alpha NP-RNP@DMN, and fabricated it as a transdermal drug delivery system. This well -designed microneedle patch, endowed with efficient tumor drug delivery ability, was able to mature tumor -infiltrating dendritic cells (TIDCs) and further promote the infiltration of CD8+ T cells into the tumor tissue with the aid of R848. Moreover, the introduction of aPD-1 blocked the programmed cell death protein 1/programmed cell death ligand 1(PD-1/PD-L1) immune checkpoints, synergistically reversing the immunosuppressive microenvironment of TNBC. In vivo therapeutic results demonstrated that alpha NP-RNP@DMN not only significantly prolonged the survival time of 4T1 tumor -bearing mice, but also inhibited tumor recurrence and lung metastasis after surgery, implying the great potential of this effective drug delivery system for enhanced immunotherapy of superficial tumors.