Applications of Polyaniline-Based Molybdenum Disulfide Nanoparticles against Brain-Eating Amoebae

Abstract

Primary amoebic meningoencephalitis and granulomatous amoebic encephalitis are distressing infections of the central nervous system caused by brain-eating amoebae, namely, Naegleria fowleri and Acanthamoeba spp., respectively, and present mortality rates of over 90%. No single drug has been approved for use against these infections, and current therapy is met with an array of obstacles including high toxicity and limited specificity. Thus, the development of alternative effective chemotherapeutic agents for the management of infections due to brain-eating amoebae is a crucial requirement to avert future mortalities. In this paper, we synthesized a conducting polymer-based nanocomposite entailing polyaniline (PANI) and molybdenum disulfide (MoS 2 ) and explored its anti-trophozoite and anti-cyst potentials against Acanthamoeba castellanii and Naegleria fowleri. The intracellular generation of reactive oxygen species (ROS) and ultrastructural appearances of amoeba were also evaluated with treatment. Throughout, treatment with the 1:2 and 1:5 ratios of PANI/MoS 2 at 100 μg/mL demonstrated significant anti-amoebic effects toward A. castellanii as well as N. fowleri, appraised to be ROS mediated and effectuate physical alterations to amoeba morphology. Further, cytocompatibility toward human keratinocyte skin cells (HaCaT) and primary human corneal epithelial cells (pHCEC) was noted. For the first time, polymer-based nanocomposites such as PANI/MoS 2 are reported in this study as appealing options in the drug discovery for brain-eating amoebae infections.

Amebicides against Acanthamoeba castellanii: The Impact of Organism Models Used in Amebicide Assays

“…It should be noted that the use of nanocoating (five studies investigating amphotericin B, glimepiride, vildagliptin, repaglinide, metformin, tannic acid, and irosustat; Table 3) is an alternative for substances that have good amoebicidal values and high toxicity to mammal cells [57,61,63,67]. This is one of the most promising methods to treat keratitis, as the ocular tissue is an extremely sensitive region.…”

“…It can also be concluded in Table 3 that in vitro studies are not exact representations of acanthamoebiasis0associated cells since many analyses used model systems as macrophages and the immortalized Henrietta lacks cervical adenocarcinoma cells (HeLa cells), such that the choice of cells impairs the advancement of in vivo toxicity studies. Just five studies used a representative cell line for ocular HCE cells to test drug toxicity (Table 3) [50,51,58,59,63]. Thus, more studies are necessary using cell models that are representative of the A. castellanii infection (keratitis and granulomatous amoebic encephalitis) [50,51,58,59,63].…”

“…Just five studies used a representative cell line for ocular HCE cells to test drug toxicity (Table 3) [50,51,58,59,63]. Thus, more studies are necessary using cell models that are representative of the A. castellanii infection (keratitis and granulomatous amoebic encephalitis) [50,51,58,59,63]. The primary, immortalized, and transformed HCE and cerebral cortical cells are recommended, and 3D multilayer systems reconstructed from human corneal or brain tissues should be of value in the analysis of anti-A.…”