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

Menka Khoobchandani,Ademar B Lugão,Kattesh V Katti,Velaphi C Thipe,Michael B Nicholl,Chetan P Hans,Kavita K Katti,Aslam Khan,Amal Y Al-Yasiri,Darsha K D Mohandoss

doi:10.1038/s41598-021-96224-8

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.

Highlights

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
In view of the extraordinary importance of immunomodulatory intervention in treating mCRPC, we focused our attention on the creation of Mangiferin encapsulated gold nanoparticles (MGF-AuNPs)
Full characterization details of MGF-AuNPs using combinations of techniques including UV–visible Spectrophotometry, Dynamic Light Scattering (DLS), Transmission Electron Microscopy (TEM), Inductively Coupled Plasma Mass Spectrometry (ICP-MS), Energy-Dispersive X-ray Spectroscopy (EDS) and Powder X ray Diffraction (PXRD)—are all outlined in the supplementary materials section (Figures S1–S4)

Summary

Introduction

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. 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 (IL12 and TNF-α) with concomitant reductions in the levels of pro-tumor cytokines (IL-10 and IL-6). 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. Myeloid-derived suppressor cells (MDSCs) induce an immune suppressive microenvironment and promote the M2-polarized tumor associated macrophages (TAMs). The polarization and differentiation of macrophages into the cancer-inhibiting M1 and cancer-promoting M2 phenotypes represent the two states of macrophages in the tumor microenvironment[8,9,10]

Methods

Results

Conclusion