Tissue-Resident Macrophage Membrane-Coated Nanomedicine for Targeted Tumor Therapy

Nanoparticles (NPs) coated with macrophage membranes have recently emerged as promising tools in nanomedicine due to their properties, including immune evasion, extended blood circulation, cell-specific targeting, and precise molecular recognition. Recently, the view of classification of macrophages into M1 and M2 types has been considered overly simplistic, as it overlooks the complexity of different kinds of tumor microenvironment. However, most current systems utilize M1-type macrophages as membrane sources, raising concerns about their tumor promoting potential, and tumor barriers restrict direct drug diffusion. In contrast, tissue-resident macrophages represent a promising approach for developing tumor targeting nanodevices. Their tissue-specific homing ability allows them to bypass immune surveillance and migrate to sites of inflammation. Furthermore, they possess a significant capacity to regulate T cell immune function, influencing tumor progression and maintaining tissue homeostasis. These targeting and immunomodulatory capabilities are attributed to the surface expression of tissue-specific biomolecules. Membrane-coated nano delivery systems derived from tissue macrophages offer enhanced therapeutic efficacy and safety by promoting prolonged circulation and improving drug accumulation at target sites. This review highlights the advantages and future potential of using tissue-resident macrophage membranes as multifunctional biomimetic surface functionalization for nanoparticle camouflaging in tumor therapy. It also examines the origins of tissue macrophages, their roles in T cell immune regulation, and strategies for engineering macrophage membrane-coated nanoparticles, with a focus on fabrication types and therapeutic prospects.