Nanoengineered M1 macrophages enhance photodynamic therapy of melanoma through oxygen production and subsequent antitumor immunity

Abstract

Photodynamic therapy (PDT) is an emerging treatment for melanoma stimulating antitumor immune responses. However, oxygen consumption by PDT exacerbates hypoxia and immunosuppression in the tumor microenvironment. This issue could potentially be addressed by M1 macrophages with high hydrogen peroxide concentrations, which can be catalyzed to oxygen, thereby increasing oxygen level and enhancing intrinsic immune response of M1 macrophages and their ability to stimulate adaptive immunity. Herein, biocompatible photosensitizer-containing nanoparticles were designed by combining bovine serum albumin and manganese dioxide (BMB). These nanoparticles were internalized by M1 macrophages in vitro to form nanoengineered macrophages (BMB@M1). BMB@M1 demonstrated various ways to transfer nanoparticles in melanoma with high tumor site accumulation. Within the tumor microenvironment characterized by hydrogen peroxide and acidity, BMB underwent Mn2+ transformation and generated oxygen. The paramagnetic property of Mn2+ was used for magnetic resonance imaging, enabling visualization of the melanoma enrichment process of BMB@M1. Oxygen supplementation enhanced the therapeutic effect of PDT and stimulated the secretion of IL-12 and IFN-γ by macrophages, synergistically promoting the infiltration of T cells and dendritic cells into the tumor. These findings showed that nanoengineered M1 macrophage could be used as a delivery system to enhance immune effects of PDT.