Biomimetic manganese-eumelanin nanocomposites for combined hyperthermia-immunotherapy against prostate cancer

Journal of Nanobiotechnology

Jie Tian¹  Pengli Gao¹  Yu Liu¹  Wei Zhang²  Kunxiong Guo²  Jun Wu²  Wenting Shang²  Hui Hui²  Heng Liu³  Yanli Guo⁴ 

[1]Beijing Advanced Innovation Center for Big Data-Based Precision Medicine, School of Medicine and Engineering, Beihang University

[2]CAS Key Laboratory of Molecular Imaging, Beijing Key Laboratory of Molecular Imaging, The State Key Laboratory of Management and Control for Complex Systems, Institute of Automation, Chinese Academy of Sciences

[3]Department of Radiology, PLA Rocket Force Characteristic Medical Center

[4]Department of Ultrasound, Southwest Hospital, Army Medical University

关键词: Tumor-associated macrophages;    Immunomodulation;    Hyperthermia-immunotherapy;    Eumelanin;    Prostate cancer;   

DOI  :  10.1186/s12951-022-01248-5

来源: DOAJ

【 摘 要 】

Abstract 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. Graphical Abstract

【 授权许可】

Unknown