Pro-tumoral and immunosuppressive M2-like tumor-associated macrophages (TAMs) contribute to
tumor progression, recurrence and distal
metastasis. However, current TAMs-modulating therapeutic strategies often encounter challenges including insufficient immune activation, weak antigen presentation ability and unsatisfactory antitumor immune performance. Herein,
cyclic RGD peptide functionalized and
manganese doped
eumelanin-like nanocomposites (RMnMels) are reported for combined
hyperthermia-
immunotherapy against PC3
prostate cancer. The RMnMels could promote M2-to-M1 macrophage repolarization via scavenging multiple
reactive oxygen species and remodeling the immunosuppressive tumor microenvironment. Following near-infrared light irradiation, RMnMels-mediated thermal ablation not only could destroy
tumor cells directly, but also elicit the release of damage associated molecular patterns and
tumor-associated
antigens, provoking robust
tumor immunogenicity and strong antitumor immune responses. The results showed that RMnMels could effectively scavenge
reactive oxygen species and promote M2-to-M1 macrophage repolarization both in vitro and in vivo. Synergistically enhanced anti-
tumor therapeutic efficacy was achieved following single administration of RMnMels plus single round of
laser irradiation, evidenced by decreased primary
tumor sizes and decreased number of distant liver metastatic nodules. The as-developed RMnMels may represent a simple and high-performance therapeutic nanoplatform for
immunomodulation and enhanced antitumor immune responses.