Nanomelanin Potentially Protects the Spleen from Radiotherapy-Associated Damage and Enhances Immunoactivity in Tumor-Bearing Mice

Abstract

Radiotherapy side-effects present serious problems in cancer treatment. Melanin, a natural polymer with low toxicity, is considered as a potential radio-protector; however, its application as an agent against irradiation during cancer treatment has still received little attention. In this study, nanomelanin particles were prepared, characterized and applied in protecting the spleens of tumor-bearing mice irradiated with X-rays. These nanoparticles had sizes varying in the range of 80–200 nm and contained several important functional groups such as carboxyl (-COO), carbonyl (-C=O) and hydroxyl (-OH) groups on the surfaces. Tumor-bearing mice were treated with nanomelanin at a concentration of 40 mg/kg before irradiating with a single dose of 6.0 Gray of X-ray at a high dose rate (1.0 Gray/min). Impressively, X-ray caused mild splenic fibrosis in 40% of nanomelanin-protected mice, whereas severe fibrosis was observed in 100% of mice treated with X-ray alone. Treatment with nanomelanin also partly rescued the volume and weight of mouse spleens from irradiation through promoting the transcription levels of splenic Interleukin-2 (IL-2) and Tumor Necrosis Factor alpha (TNF-α). More interestingly, splenic T cell and dendritic cell populations were 1.91 and 1.64-fold higher in nanomelanin-treated mice than those in mice which received X-ray alone. Consistently, the percentage of lymphocytes was also significantly greater in blood from nanomelanin-treated mice. In addition, nanomelanin might indirectly induce apoptosis in tumor tissues via activation of TNF-α, Bax, and Caspase-3 genes. In summary, our results demonstrate that nanomelanin protects spleens from X-ray irradiation and consequently enhances immunoactivity in tumor-bearing mice; therefore, we present nanomelanin as a potential protector against damage from radiotherapy in cancer treatment.

Microbial production of melanin and its various applications

“…Moreover, melanization is considered a survival strategy for many organisms inhabiting unfavorable environmental conditions. Owing to the multifunctionality of the pigment, it has been known to serve as: (a) an antioxidant and radical scavenger (Ju et al 2011 ; Le Na et al 2019 ), (b) a photo-protector that efficiently absorbs and dissipates solar radiation in the form of heat (d’Ischia et al 2015 ), (c) an absorber that chelates metals and binds organic compounds (Karlsson and Lindquist 2016 ; Tran-Ly et al 2020 ) and (d) an organic semiconductor (Bothma et al 2008 ). Besides these functions, melanin is considered eco-friendly and biocompatible since it is naturally synthesized by most organisms.…”

Excessive splenic volume is an unfavorable prognostic factor in patients with non-small cell lung cancer treated with chemoradiotherapy

“…Some studies have suggested that splenic irradiation can cause radiation-related lymphopenia and damage the immune function, which adversely affects the body. [ 23 , 24 ] However, some studies have indicated that radiation-related lymphopenia does not affect the overall survival rate of patients. [ 17 ] Some studies suggest that tumor irradiation combined with spleen irradiation can result in additional T cell aggregation in the tumor microenvironment, which assists with controlling tumors.…”

Melanin and Melanin-Functionalized Nanoparticles as Promising Tools in Cancer Research—A Review

“…MEL-NPs can be produced both by biological extraction, which resorts to the direct separation and purification of spherical NPs from natural sources, and chemical synthesis. For instance, Le Na et al obtained nanomelanin particles by dissolving commercial melanin powder in alkaline solvents (i.e., sodium and/or ammonium hydroxide) and neutralizing the solution using hydrochloride acid [ 92 ]. Artificially synthesized polydopamine nanoparticles (PDA-NPs) mimic natural melanin, possessing similar properties but provide better controllability.…”