Mesoporous polydopamine-based nanodrug delivery systems for tumor immunotherapy.

Abstract

Mesoporous polydopamine (MPDA) nanocarriers exhibit significant advantages in tumor drug delivery and immunotherapy owing to their well-defined mesoporous structure, modifiable surface chemistry, environmentally responsive degradation, and efficient photothermal properties. MPDA nanoparticles possess a high specific surface area and tunable pore channels, enabling efficient loading and controlled release of various therapeutic molecules. The abundant catechol and amine groups on their surface facilitate convenient functionalization, which is beneficial for targeted modification. The photothermal effect triggered by near-infrared laser irradiation not only enables localized tumor ablation but also induces immunogenic cell death, thereby activating antitumor immune responses. The acid-responsive degradation behavior of MPDA in the tumor microenvironment allows controlled drug release, while its degradation products can further promote macrophage phenotype reprogramming, thereby improving the immune microenvironment. By loading immune checkpoint inhibitors, immune adjuvants, and metabolic regulatory molecules, MPDA-based nanosystems can effectively alleviate tumor-induced immunosuppression and enhance immunotherapy responses. Additionally, this platform can optimize lymphatic transport efficiency, promote nanoparticle accumulation in draining lymph nodes, and subsequently facilitate dendritic cell maturation and effector T-cell activation. Although previous reviews have summarized the preparation methods and biomedical applications of MPDA-based nanoplatforms, a systematic review of their roles in modulating the tumor immune microenvironment and enhancing antitumor immune responses remains limited. Therefore, this review summarizes the latest advances in MPDA-based nanodrug delivery systems for cancer immunotherapy, with a particular focus on their immunomodulatory mechanisms and applications in multimodal synergistic cancer immunotherapy, aiming to provide insights into future development and clinical translation of MPDA nanotherapeutic systems.