Innovating Leishmaniasis Treatment: A Critical Chemist's Review of Inorganic Nanomaterials

Abstract

Leishmaniasis, a critical Neglected Tropical Disease caused by Leishmania protozoa, represents a significant global health risk, particularly in resource-limited regions. Conventional treatments are effective but suffer from serious limitations, such as toxicity, prolonged treatment courses, and rising drug resistance. Herein, we highlight the potential of inorganic nanomaterials as an innovative approach to enhance Leishmaniasis therapy, aligning with the One Health concept by considering these treatments' environmental, veterinary, and public health impacts. By leveraging the adjustable properties of these nanomaterials─including size, shape, and surface charge, tailored treatments for various diseases can be developed that are less harmful to the environment and nontarget species. We review recent advances in metal-, oxide-, and carbon-based nanomaterials for combating Leishmaniasis, examining their mechanisms of action and their dual use as standalone treatments or drug delivery systems. Our analysis highlights a promising yet underexplored frontier in employing these materials for more holistic and effective disease management.

Keywords: Leishmaniasis; carbon-based materials; drug delivery systems; inorganic nanomaterials; metallic nanoparticles; neglected tropical diseases; oxide nanoparticles.

Figure 1

Most common drugs used in the treatment of Leishmaniasis.

Figure 2

Leishmania parasite life cycle. (A) The promastigote form of Leishmania enters the mammalian host through the bite of an infected sandfly. (B) Once inside the host, the promastigotes are phagocytized by macrophage. (C) Within the macrophage, promastigotes transform into amastigotes, and (D) they reproduce within the macrophage until it bursts. (E) Subsequently, the amastigote form disseminates throughout the body, and eventually (F) they undergo differentiation back into promastigotes.

Figure 3

Mechanism of ROS production inside macrophages by the oxidation of metallic nanoparticles. Once in the body, the NPs (A) are recognized as foreign bodies and (B) are phagocytized by the macrophages. Inside the macrophage, (C) the NPs undergo surface oxidation (indicated by the change of color), thus producing ROS and NPs size reduction.

Figure 4

Fluorescence microscopy images of intramacrophage L. mexicana treated with AuNP, AmpoB@AuNP and pure AmB (AmpoB), in which the red fluorescence is related to infected macrophages, and the blue fluorescence is the nucleus. The treatment with 0.25 μg mL^–1 AmpoB@AuNP was able to inhibit parasite infection by enabling AmB internalization. Adapted with permission from ref (54). Copyright 2021 John Wiley and Sons.

Figure 5

(A) Synthetic scheme of the AgNPs reduced by dill leaf extract and further combination with antileishmanial drug miltefosine. (B) SEM images showing the morphological changes in the promastigotes treated with the AgNP-miltefosine combination. Adapted with permission from ref (94). Copyright 2016 Elsevier.

Figure 6

Mechanisms to generate ROS by light irradiation of the MO-NPs.

Figure 7

Schematic illustration of the γ-Fe₂O₃ NPs functionalized with Ce^3/4+ complex coordinated by both PEI and pentamidine ligands, developed by Kannan and co-workers. Reproduced from ref (30). Copyright 2021 American Chemical Society.

Figure 8

Number of trials using inorganic nanoparticles according to the type of NPs and their current clinical phase.