Macrophage-Mediated Delivery of Multifunctional Nanotherapeutics for Synergistic Chemo–Photothermal Therapy of Solid Tumors

Although great efforts have been undertaken to develop a nanoparticle-based drug delivery system (DDS) for the treatment of solid tumors, the therapeutic outcomes are still limited. Immune cells, which possess an intrinsic ability to phagocytose nanoparticles and are recruited by tumors, can be exploited to deliver nanotherapeutics deep inside the tumors. Photothermal therapy using near-infrared light is a promising noninvasive approach for solid tumor ablation, especially when combined with chemotherapy. In this study, we design and evaluate a macrophage-based, multiple nanotherapeutics DDS, involving the phagocytosis by macrophages of both small-sized gold nanorods and anticancer drug-containing nanoliposomes. The aim is to treat solid tumors, utilizing the tumor-infiltrating properties of macrophages with synergistic photothermal-chemotherapy. Using a 3D cancer spheroid as an in vitro solid tumor model, we show that tumor penetration and coverage of the nanoparticles are both markedly enhanced when the macrophages are used. In addition, in vivo experiments involving both local and systemic administrations in breast tumor-bearing mice demonstrate that the proposed DDS can effectively target and kill the tumors, especially when the synergistic therapy is used. Consequently, this immune cell-based theranostic strategy may represent a potentially important advancement in the treatment of solid tumors.