PLGA-based nanoparticles in colorectal cancer immunotherapy: current concepts and future perspectives

Colorectal cancer (CRC) remains a leading cause of cancer mortality, and the benefits of immune checkpoint inhibitors are largely confined to the dMMR/MSI-H minority, underscoring the need to remodel the immunosuppressive tumor microenvironment (TME). Poly (lactic-co-glycolic acid) (PLGA) nanoparticles offer biodegradable, tunable carriers with high payload capacity and amenability to targeting, enabling precise delivery and controlled release of immunomodulators. In CRC, these platforms can enhance antigen capture and presentation, recondition suppressive myeloid networks, and coordinate checkpoint blockade with complementary therapeutics to strengthen antitumor immunity and restrain tumor growth. In this review, we summarize current principles for PLGA nanoparticles-based immunotherapies, emphasizing payload selection, release kinetics, microenvironmental responsiveness, and spatiotemporal targeting in CRC. We also outline translational considerations encompassing safety, pharmacokinetics, manufacturability, and regulatory readiness. Addressing these factors may accelerate clinical deployment of PLGA-enabled strategies and extend the benefits of immunotherapy in CRC patients.