Recent advances in PD-L1 siRNA nanocarriers for cancer therapy

Tumor immune evasion depends on the programmed death-ligand 1 (PD-L1) mechanism, making it a prominent target in cancer therapy. Small interfering RNA (siRNA) designed to inhibit PD-L1 expression presents an innovative approach for boosting immunity against tumors. However, the therapeutic use of siRNA faces challenges, primarily due to its instability and inefficient cellular delivery. Recent advancements in nanocarrier technologies have shown promise in overcoming these obstacles, improving the delivery and efficacy of PD-L1 siRNA. This review comprehensively explores various nanocarrier systems, including lipid nanoparticles, polymeric carriers, and inorganic nanoparticles, highlighting their design innovations and applications in targeting PD-L1 in diverse cancer models. We discuss the synergistic effects of PD-L1 siRNA delivered via nanocarriers in conjunction with chemotherapy and immunomodulators, showcasing their potential to boost immune responses and reduce tumor growth. Additionally, we address ongoing challenges such as optimizing biodistribution and minimizing off-target effects, which hinder clinical translation. By synthesizing recent research findings, this review aims to illuminate the transformative potential of PD-L1 siRNA nanocarriers in cancer immunotherapy, paving the way for future studies aimed at enhancing therapeutic strategies and improving patient outcomes.