Iron chelated melanin-like nanoparticles for tumor-associated macrophage repolarization and cancer therapy

Abstract

Tumor-associated macrophages (TAMs) are abundant in many cancers, and predominately display an immunosuppressive M2-like function that fosters tumor progression and promotes malignant metastasis. Current TAMs repolarization strategies mainly focused on harnessing the direct cancer cell killing property of M1-like macrophages repolarized from TAMs. However, the latent role of M1-like macrophages as professional antigen-presenting cells (APCs) also needs to be explored. Here, iron chelated melanin-like nanoparticles (Fe@PDA-PEG) were developed for M2-to-M1 TAMs repolarization and photothermal therapy (PTT) induced tumor-associated antigens (TAAs) releasing, which would exploit the potential of M1-like macrophages acquired as professional APCs for TAAs presentation. The results showed that M1 macrophages repolarized from TAMs by Fe@PDA-PEG could capture, process and present TAAs released by PTT through the major histocompatibility complex class II (MHC II) pathway, recruiting T-helper cells and effector T cells in tumor site, which leads to the controlled tumor growth and limited malignant metastasis.

Keywords: Antigen presentation; Cancer therapy; Immunotherapy; Macrophage repolarization; Metastasis; Tumor-associated macrophages.