Nanoparticle-based methionine and AICAR delivery elicits a robust antitumor immune response

Abstract

Immunotherapy uses the immune system's intrinsic defense mechanisms to destroy malignancies and has garnered increasing interest in recent years. The main objectives of immunotherapy are activating immune cells and forming a strong antitumor immune response. The tumor microenvironment (TME) is a complex ecology full of chemicals that can substantially affect immune cell activity, especially the function of CD4⁺ T cells. In this study, we produced an artificial nanoparticle (NP) comprising methionine and AICAR with PD-1 antibodies attached to its surface, targeted at increasing effector immune responses by directly altering the TME. By targeting PD-1 receptors, this coloaded NP effectively travels to the tumor site and activates CD4⁺ T cells within the TME. After receiving these NPs, the mice's tumor-infiltrating CD4⁺ T cells expressed less PD-1, and their Th1-driven antitumor immunity increased. These effects resulted in substantial tumor inhibition. Our findings suggest that this NP-based technique, which direct regulates the TME, has the potential as a robust tool to enhance anticancer efficacy by promoting immune cell activation within the TME.