Macrophage membrane-coated gelatin/laponite nanoparticles containing doxorubicin for anticancer immunotherapy

Abstract Objectives To enhance cancer immunotherapy specificity and evade immune clearance, we developed MGLD (Macrophage membrane/gelatin/laponite/doxorubicin) nanoparticles (≈130 nm) encapsulated with doxorubicin. This system aims to improve tumor targeting, prevent immune clearance, and induce autophagy and immunogenic cell death (ICD) in cancer cells. Methods MGLD nanoparticles were engineered with macrophage membranes to reduce immune system phagocytosis and enhance tumor targeting. In vitro and in vivo assays evaluated the nanoparticles’ accumulation, penetration, cytotoxicity in tumor tissues, and ability to induce immunogenic cell death (ICD). Results MGLD nanoparticles accumulated in tumors, penetrated deep into tissues, and induced ICD. Acidic tumor microenvironment and MMP-2 facilitated rapid DOX release, enhancing anticancer efficacy with minimal macrophage toxicity. MGLD showed excellent stability, pH sensitivity, and negligible in vivo toxicity, stimulating autophagy and ICD. Conclusions The results demonstrate that MGLD nanoparticles are a promising candidate for targeted cancer therapy. This biomimetic system enhances drug targeting and efficacy, overcoming the limitations of conventional chemotherapy and offering a transformative therapeutic strategy.