Sialic acid conjugate-modified liposomal platform modulates immunosuppressive tumor microenvironment in multiple ways for improved immune checkpoint blockade therapy

Insights into the Role of Sialylation in Cancer Metastasis, Immunity, and Therapeutic Opportunity

“…Intriguingly, the ligand effects of sialic acids can be utilized in the development of drug delivery systems. The sialic acid-cholesterol conjugate liposomal vehicle has been reported to be an effective targeting drug delivery strategy [ 160 , 161 ]. Chemoimmunotherapy is enhanced by the administration of doxorubicin, metformin, and anti-PD-1 monoclonal antibody using this sialic acid-based liposomal platform [ 160 ].…”

“…The sialic acid-cholesterol conjugate liposomal vehicle has been reported to be an effective targeting drug delivery strategy [ 160 , 161 ]. Chemoimmunotherapy is enhanced by the administration of doxorubicin, metformin, and anti-PD-1 monoclonal antibody using this sialic acid-based liposomal platform [ 160 ]. This drug delivery system also increases the uptake of epirubicin by TAMs, resulting in the depletion of TAMs and the suppression of tumor development [ 161 ].…”

Sialic acid-mediated photochemotherapy enhances infiltration of CD8+ T cells from tumor-draining lymph nodes into tumors of immunosenescent mice

“…Photodynamic/Photothermal therapy (PDT/PTT) increased the accumulation of SA-modified NPs in the tumor by enhancing tumor infiltration by neutrophils 19 . SA-modified DOX liposomes prepared in our laboratory-induced the expression of calreticulin (CRT), increased the secretion of HMGB-1, and promoted the release of ATP from tumor cells 20 . Dendritic cells recognize and phagocytize tumor cells, enhance the ability of CD8 + T cells to infiltrate tumors, and attack the tumor cells 21 .…”

Targeting Ibrutinib to Tumor-Infiltrating T Cells with a Sialic Acid Conjugate-Modified Phospholipid Complex for Improved Tumor Immunotherapy

“…Immunotherapy for advanced and metastatic cancers has attracted widespread attention in recent years. − Important examples of this include immune checkpoint blockade (ICB) therapy, targeting either programed death ligand-1 (PD-L1) or programed death-1 (PD-1), which has triggered long-term antitumor immune responses and achieved durable tumor regression in clinical trials. , Despite its promise, the development of complementary strategies to enhance the proportion of patients achieving benefits from ICB therapy remains a formidable challenge. , Several small-molecule therapeutics that target relevant signaling pathways in the immunosuppressive tumor microenvironment have been exploited in combination with ICB treatment. − …”

“…4,5 Despite its promise, the development of complementary strategies to enhance the proportion of patients achieving benefits from ICB therapy remains a formidable challenge. 6,7 Several small-molecule therapeutics that target relevant signaling pathways in the immunosuppressive tumor microenvironment have been exploited in combination with ICB treatment. 8−10 Ibrutinib (IBR), a confirmed covalent inhibitor of Bruton's tyrosine kinase (BTK), has been approved as a clinical therapy for B-cell malignancies such as mantle cell lymphoma and chronic lymphocytic leukemia.…”