bis(3--5-)-cyclic-diguanylic-acid and 1-2-oleoylphosphatidylcholine

To alter the immunosuppressive tumor microenvironment (TME), we developed an immunostimulatory nanoparticle (NP) to reprogram a tumor's dysfunctional and inhibitory antigen-presenting cells (APCs) into properly activated APCs that stimulate tumor-reactive cytotoxic T cells. Importantly, systemic delivery allowed NPs to efficiently utilize the entire microvasculature and gain access into the majority of the perivascular TME, which coincided with the APC-rich tumor areas leading to uptake of the NPs predominantly by APCs. In this work, a 60 nm NP was loaded with a STING agonist, which triggered robust production of interferon β, resulting in activation of APCs. In addition to untargeted NPs, we employed 'mainstream' ligands targeting fibronectin, α

Topics: 1,2-Dipalmitoylphosphatidylcholine; Animals; Breast Neoplasms; Cell Line, Tumor; Cyclic GMP; Dendritic Cells; Immunity, Innate; Immunologic Factors; Ligands; Macrophages; Mice, Inbred BALB C; Nanoparticles; Peptides; Phosphatidylcholines; Phosphatidylethanolamines; Polyethylene Glycols; T-Lymphocytes; Tumor Microenvironment