Macrophage hitchhiking for smart nanomedicine: Bridging immune navigation and targeted therapy

The intrinsic abilities of macrophages, including innate homing, robust phagocytic capacity, and phenotypic plasticity, make them ideal candidates for targeted drug delivery. By utilizing macrophages as carriers, nanoparticles can be precisely transported to specific physiological sites, enhancing therapeutic efficacy and minimizing off-target effects. This strategy, known as the "macrophages hitchhiking", leverages the natural capabilities of macrophages to traverse biological barriers. The review comprehensively explores the role of macrophages in the pathogenesis of various diseases, highlighting their potential as vehicles for therapeutic interventions. It meticulously categorizes and summarizes the diverse array of nanoparticles that exploit macrophages for targeted delivery. The discussion elaborates on the design of nanoparticles aimed at enhancing macrophage uptake, facilitating the controlled release of therapeutic agents, with a systematic review of the applications. Additionally, the review provides an in-depth analysis of the advantages, limitations, and future directions of this approach. The transformative potential in personalized medicine is underscored, particularly in addressing scalability challenges and advancing the clinical translation of macrophage-targeted nanoparticles. Finally, the potential applications of the macrophage hitchhiking strategy for in situ CAR-Macrophage therapy were proposed. The review aims to catalyze the development of next-generation therapies and pave the way for more precise and effective treatment modalities.