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An Orthotopic Murine Model of Human Prostate Cancer Metastasis
Published on: September 18, 2013
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.
Abstract:
Men with castration-resistant prostate cancer (CRPC) face poor prognosis and increased risk of treatment-incurred adverse effects resulting in one of the highest mortalities among patient population globally. Immune cells act as double-edged sword depending on the tumor microenvironment, which leads to increased infiltration of pro-tumor (M2) macrophages. Development of new immunomodulatory therapeutic agents capable of targeting the tumor microenvironment, and hence orchestrating the transformation of pro-tumor M2 macrophages to anti-tumor M1, would substantially improve treatment outcomes of CRPC patients. We report, herein, Mangiferin functionalized gold nanoparticulate agent (MGF-AuNPs) and its immunomodulatory characteristics in treating prostate cancer. We provide evidence of immunomodulatory intervention of MGF-AuNPs in prostate cancers through observations of enhanced levels of anti-tumor cytokines (IL-12 and TNF-α) with concomitant reductions in the levels of pro-tumor cytokines (IL-10 and IL-6). In the MGF-AuNPs treated groups, IL-12 was elevated to ten-fold while TNF-α was elevated to about 50-fold, while IL-10 and IL-6 were reduced by two-fold. Ability of MGF-AuNPs to target splenic macrophages is invoked via targeting of NF-kB signaling pathway. Finally, therapeutic efficacy of MGF-AuNPs, in treating prostate cancer in vivo in tumor bearing mice, is described taking into consideration various immunomodulatory interventions triggered by this green nanotechnology-based nanomedicine agent.
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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