Interaction of PEGylated gold nanorods with HIF-1α/Ki-67 in inhibiting immunosuppression and arresting cancer proliferation in murine fibrosarcoma.

Gold nanoparticles have shown great promise as potential theranostic agents. Interaction of gold nanoparticles with the primary organs of the reticulo-endothelial system (RES), known for their immunoregulatory functions, has not been adequately explored in animal models of solid tumors. In this study, we chose fibrosarcoma as a representative solid tumor model, as it frequently metastasizes to distant RES organs such as the spleen and liver. This paper investigates the effect of polyethylene glycol (PEG)-functionalized gold nanorods (GNRs) of an aspect ratio of 2.5, in spleen and liver-two vital organs of the RES that serve as distant metastatic sites for fibrosarcoma. Here, we study the ability of PEG-GNRs to attenuate hypoxia-driven proliferation and immunosuppression while inducing apoptotic remodeling in RES organs. Uptake of PEG-GNRs significantly decreased Ki-67 expression (a molecular marker of cancer progression) by attenuation of hypoxia-inducing factor 1-alpha (HIF-1α). Upregulation of HIF-1α favours development of solid tumor and its progression. In addition, HIF-1α is an important regulator of cytokine production, viz. TNF-α, IL-1β, IL-10, which, along with oxidative measurements, showed a decline in cancer progression upon PEG-GNR treatment, while improved tissue structure was confirmed by H&E staining. However, treatment showed increase of IL-12, an anti-tumorigenic cytokine, supporting macrophage plasticity toward an M1 phenotype. Further, through TEM imaging and upregulation of caspase-3 we confirmed PEG-GNR induced apoptosis. Our study reports that PEG-GNRs selectively inhibit the growth of cancer cells, rarely causing toxicity to normal cells, as supported by both comet and micronuclei assay.