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

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

Immunotherapeutic Value of Transcription Factor 19 (TCF19) Associated with Renal Clear Cell Carcinoma: A Comprehensive Analysis of 33 Human Cancer Cases

“…Macrophages are polarized by the stimulation of transcription factors in the tumor microenvironment by controlling their antitumor activity and by affecting their immunotherapy [ 23 , 24 ]. Our previous study also confirmed that changes in macrophage polarization play substantial activities to regulate the inflammatory traumatic urethral stricture [ 25 ] and resistance to chemotherapy and endocrine therapy in advanced prostate cancer [ 26 ]. In general, TCF family genes significantly influence the immune system and the state of tumor tissue.…”

“…Another study recently reported that M2-tumor-associated macrophages (TAMs) were able to promote the process of bone metastasis and were able to influence the chemotherapy and drug resistance ability of the cells of prostate cancer. The regulation of the process of macrophage polarization can influence the effect of immunotherapy in patients suffering from prostate cancer [ 26 ]. Sen, Yang GH, and Mondal reported that TCF19, a novel pancreatic islet regulator, regulated the processes of energy metabolism and stress adaptation associated with the tumor cells by regulating gluconeogenesis.…”

Manganese-based nanomaterials promote synergistic photo-immunotherapy: green synthesis, underlying mechanisms, and multiple applications

“…Photothermal-induced ICD effect can cooperate with the immune stimulation of Mn 2+ to jointly change TME and improve the therapeutic effect of cancer. 147 PTT ablates tumor cells by local heating. However, this may cause damage to adjacent normal tissues.…”

Intrinsically Bioactive Manganese–Eumelanin Nanocomposites Mediated Antioxidation and Anti‐Neuroinflammation for Targeted Theranostics of Traumatic Brain Injury

“…Along with these fascinating features, MelNPs also exhibit excellent metal ion chelating ability for high binding affinity toward various paramagnetic metal ions, such as iron, manganese, and gadolinium, as MR contrast agents. [17,22] By doing so in vivo distribution and targeting ability of nanoparticles in lesions could be monitored dynamically. In addition, targeted molecules are integrated to the surface of MelNPs by conjugating with abundant functional groups, such as angiopep-2.…”