Comparison of the uptake of untargeted and targeted immunostimulatory nanoparticles by immune cells in the microenvironment of metastatic breast cancer.

ABSTRACT: 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_vβ₃ integrin and P-sel

SUBMITTER: Covarrubias G 

PROVIDER: S-EPMC8732314 | biostudies-literature | 2022 Jan

REPOSITORIES: biostudies-literature