Green nanotechnology of MGF-AuNPs for immunomodulatory intervention in prostate cancer therapy

Menka Khoobchandani1,2, Aslam Khan3, Kavita K Katti1

  • 1Department of Radiology, Institute of Green Nanotechnology, University of Missouri, Columbia, MO, 65212, USA.

Scientific Reports
|August 19, 2021
PubMed

Insights

Mangiferin functionalized gold nanoparticles (MGF-AuNPs) show promise in treating castration-resistant prostate cancer (CRPC). This novel nanomedicine shifts immune cells to fight tumors, improving outcomes for CRPC patients.

Area of Science:

  • Nanomedicine
  • Immunology
  • Oncology

Background:

  • Castration-resistant prostate cancer (CRPC) presents a significant global health challenge with limited treatment options and high mortality.
  • The tumor microenvironment, particularly M2 macrophages, promotes CRPC progression, necessitating novel therapeutic strategies.
  • Modulating immune responses by transforming pro-tumor M2 macrophages into anti-tumor M1 macrophages is a promising approach for CRPC treatment.

Purpose of the Study:

  • To investigate the immunomodulatory characteristics and therapeutic efficacy of Mangiferin functionalized gold nanoparticulate agent (MGF-AuNPs) in prostate cancer.
  • To evaluate the potential of MGF-AuNPs to reprogram tumor-associated macrophages within the tumor microenvironment.
  • To assess the impact of MGF-AuNPs on cytokine profiles and their therapeutic effects in a preclinical model of prostate cancer.

Main Methods:

  • Synthesis and characterization of Mangiferin functionalized gold nanoparticles (MGF-AuNPs).
  • In vitro assessment of MGF-AuNPs' immunomodulatory effects on macrophage polarization and cytokine production (IL-12, TNF-α, IL-10, IL-6).
  • In vivo evaluation of MGF-AuNPs' therapeutic efficacy in a tumor-bearing mouse model, analyzing immune cell infiltration and signaling pathways (NF-kB).

Main Results:

  • MGF-AuNPs demonstrated significant immunomodulatory effects, increasing anti-tumor cytokines (IL-12 by tenfold, TNF-α by 50-fold) and decreasing pro-tumor cytokines (IL-10 and IL-6 by twofold).
  • MGF-AuNPs were shown to target splenic macrophages, likely through modulation of the NF-kB signaling pathway.
  • Therapeutic efficacy was observed in vivo, with MGF-AuNPs exhibiting anti-cancer activity mediated by triggered immunomodulatory interventions.

Conclusions:

  • MGF-AuNPs represent a promising green nanotechnology-based nanomedicine agent for modulating the tumor immune microenvironment in prostate cancer.
  • The ability of MGF-AuNPs to re-educate macrophages and alter cytokine profiles offers a novel therapeutic strategy for castration-resistant prostate cancer.
  • Further research into MGF-AuNPs could lead to improved treatment outcomes for patients with advanced prostate cancer.

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