Photodynamic/ photothermal therapy enhances neutrophil-mediated ibrutinib tumor delivery for potent tumor immunotherapy: More than one plus one?

Neutrophil-mediated drug-delivery systems have gained widespread attention owing to their superior efficacy in cancer therapy. Neutrophils, the most abundant white cells in peripheral blood, are known to migrate to inflamed tumors. Here, we elaborate on a novel strategy to enhance tumor infiltration of neutrophils by photodynamic/photothermal therapy (PDT/PTT) to deliver ibrutinib (IBR) nanocomplexes for cancer immunotherapy. DiR-loading liposomes (DiR-lipos) were administered to induce acute inflammation, and sialic acid (SA) derivative-coated IBR-loading nanocomplexes (SA-2@NCs) were fabricated for targeting activated peripheral blood neutrophils (PBNs). This in vitro and in vivo attempt, therefore, proved the hypothesis that inducing acute inflammation via PDT/PTT could facilitate the migration of PBNs, which could deliver SA-2@NCs into the tumor. The enhanced tumor delivery of SA-2@NCs was accompanied by enhanced antitumor T-cell immune responses in a mouse orthotopic breast cancer model. Our findings indicate that the combination of IBR-mediated immunotherapy with DiR-mediated PDT/PTT bring together two leading novel strategies, taking advantage of their synergistic mechanisms of action for a potent anti-tumor efficacy for breast cancer therapy.