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 differentiation of pro-tumor M2 macrophages to anti-tumor M1, would substantially improve treatment outcomes of CRPC patients. We report, herein, Mangiferin functionalized gold nanoparticles (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 treated groups, IL-12 was elevated to ten-fold while TNF-α was elevated to about fifty-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.

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The full text of this article is available to read as a PDF.
No competing interests reported.
This is a list of supplementary files associated with this preprint. Click to download.
Scheme 1: (A) Green Nanotechnology Motif of Mangiferin functionalized Gold Nanoparticles (MGF-AuNPs).
Scheme 3: Targeting ability of MGF-AuNPs toward tumor microenvironment (TME) and it’s reprograming ability of M2 to M1 phenotype.
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Posted 05 Feb, 2021
On 25 May, 2021
Received 14 May, 2021
On 28 Mar, 2021
Received 16 Mar, 2021
On 23 Feb, 2021
On 17 Feb, 2021
On 17 Feb, 2021
Invitations sent on 17 Feb, 2021
On 15 Feb, 2021
On 03 Feb, 2021
On 03 Feb, 2021
On 23 Dec, 2020
Posted 05 Feb, 2021
On 25 May, 2021
Received 14 May, 2021
On 28 Mar, 2021
Received 16 Mar, 2021
On 23 Feb, 2021
On 17 Feb, 2021
On 17 Feb, 2021
Invitations sent on 17 Feb, 2021
On 15 Feb, 2021
On 03 Feb, 2021
On 03 Feb, 2021
On 23 Dec, 2020
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 differentiation of pro-tumor M2 macrophages to anti-tumor M1, would substantially improve treatment outcomes of CRPC patients. We report, herein, Mangiferin functionalized gold nanoparticles (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 treated groups, IL-12 was elevated to ten-fold while TNF-α was elevated to about fifty-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.

Figure 1

Figure 2

Figure 3

Figure 4

Figure 5

Figure 6

Figure 7

Figure 8

Figure 9

Figure 10

Figure 11

Figure 12

Figure 13

Figure 14

Figure 15

Figure 16
The full text of this article is available to read as a PDF.
No competing interests reported.
This is a list of supplementary files associated with this preprint. Click to download.
Scheme 1: (A) Green Nanotechnology Motif of Mangiferin functionalized Gold Nanoparticles (MGF-AuNPs).
Scheme 3: Targeting ability of MGF-AuNPs toward tumor microenvironment (TME) and it’s reprograming ability of M2 to M1 phenotype.
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