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Scheme 1. Schematic illustration of Persistent immune response: Twice tumor shed induced by sialic acid–modified vincristine sulfate liposomes. (A) Preparation of SA-CH-modified vincristine sulfate liposomes. (B) Schematic illustration of SA-CH-modified vincristine sulfate liposomes, which effectively target tumor-associated macrophages, improve the tumor immunosuppressive microenvironment, and induce anti-tumor immune responses. [Display omitted] Studies have shown that tumor-associated macrophages (TAMs) are crucial for the establishment and maintenance in immunosuppressive tumor immune microenvironment (TIME), which can help tumor cells to achieve immune escape and attenuate antitumor therapy. Siglecs, the receptors of sialic acid (SA), widely exist in TAMs, which could be targeted to disrupt TIME and inhibit tumor growth at the root. Therefore, a SA–modified VCR liposome was reported (VCR-SSAL). Cellular and pharmacodynamic experiments showed that VCR-SSAL exhibited strong TAMs targeting and tumor-killing ability. Interestingly, VCR-SSAL treatment induced a phenomenon in which the cancerous tissues were "fell off" from the growth site, after which the wound gradually healed. Three months after the wound healed, the mice whose tumors fell off were re-inoculated, and the tumor fell off again without treatment, with an exfoliation rate of 100%. We speculated that this special efficacy might be due to that VCR loaded in VCR-SSAL could activate adaptive immunity by inducing DNA damage, promoting cytotoxic T lymphocytes (CTLs) infiltration into tumor sites, and enhancing the antitumor immune response. Thus, this study might provide new insights into the application of traditional chemotherapeutic drugs. [ABSTRACT FROM AUTHOR]

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. Image 1 [ABSTRACT FROM AUTHOR]