Macrophages loaded CpG and GNR-PEI for combination of tumor photothermal therapy and immunotherapy

Nano-therapeutic approach for clinical implementation of tumors remains a longstanding challenge in the medical field. The main challenges are rapid clearance, offtarget effect and the limited role in the treatment of metastatic tumors. Toward this objective, a cell-mediated strategy by transporting photothermal reagents and CpG adjuvant within macrophage vehicles is performed. The photothermal reagents are constructed by conjugating of hyperbranched polyethyleimine (PEI) to golden nanorode (GNR) via S-Au bonds. GNR-PEI/CpG nanocomposites, formed via electrostatic interaction and displayed excellent near-infrared (NIR) photothermal performance, exhibit immense macrophage uptake and negligible cytotoxic effect, which is essential for the fabrication of GNR-PEI/CpG loaded macrophages. GNR-PEI/CpG loaded macrophages demonstrated admirable photothermal response in vitro. Benefited from the functionalization of the binding adhesion between macrophages and 4T1 cells, GNR-PEI/CpG loaded macrophages significantly promoted tumor accumulation in vivo and dramatically enhanced the efficiency of photothermal cancer therapy. Moreover, the immune system is activated after photothermal therapy, which is mainly attributed to the generation of tumor specific antigens and CpG adjuvant in situ. Our findings provide a potential cell-mediated nanoplatform for tumor therapy by combination of near infrared photothermal therapy and immunotherapy.