Plant-based nanoparticles targeting malaria management

Abstract

Malaria is one of the most devastating diseases across the globe, particularly in low-income countries in Sub-Saharan Africa. The increasing incidence of malaria morbidity is mainly due to the shortcomings of preventative measures such as the lack of vaccines and inappropriate control over the parasite vector. Additionally, high mortality rates arise from therapeutic failures due to poor patient adherence and drug resistance development. Although the causative pathogen (Plasmodium spp.) is an intracellular parasite, the recommended antimalarial drugs show large volumes of distribution and low-to no-specificity towards the host cell. This leads to severe side effects that hamper patient compliance and promote the emergence of drug-resistant strains. Recent research efforts are promising to enable the discovery of new antimalarial agents; however, the lack of efficient means to achieve targeted delivery remains a concern, given the risk of further resistance development. New strategies based on green nanotechnologies are a promising avenue for malaria management due to their potential to eliminate malaria vectors (Anopheles sp.) and to encapsulate existing and emerging antimalarial agents and deliver them to different target sites. In this review we summarized studies on the use of plant-derived nanoparticles as cost-effective preventative measures against malaria parasites, starting from the vector stage. We also reviewed plant-based nanoengineering strategies to target malaria parasites, and further discussed the site-specific delivery of natural products using ligand-decorated nanoparticles that act through receptors on the host cells or malaria parasites. The exploration of traditionally established plant medicines, surface-engineered nanoparticles and the molecular targets of parasite/host cells may provide valuable insights for future discovery of antimalarial drugs and open new avenues for advancing science toward the goal of malaria eradication.

Keywords: Plasmodium spp; antimalarial drugs; green synthesis; insecticides; medicinal plants; nanoparticles; targeted drug delivery.

FIGURE 1

Schematic illustration of the Life Cycle of anopheles mosquito (A) and Transmission cycle of plasmodium parasites (B). The life cycle of the Anopheles mosquito is divided into 4 stages: the female lays eggs in swampy areas (1), these eggs develop into larvae (2) within a few days, these larvae grow and mutate into pupae (3), which mature into adult mosquitoes (4). To ensure its survival, the hematophagous Anopheles feeds on human blood, and it’s during this blood meal that the Anopheles, a vector of Plasmodium, infects humans and conducts to the transmission cycle of plasmodium in human beings. Plasmodium parasites in humans develop in two phases: hepatocytes (B’) and erythrocytes (B″) stages. In the first stage (B’), the parasite undergoes perpetual mutation from sporozoites to merozoites (1’) in liver cells, and particularly for P. ovale and P. vivax, merozoites can enter in a period of snooze, forming hypnozoites (1’’). This phase is usually asymptomatic and can last from a few hours to a few days for P. falciparum and several days for P. ovale and P. vivax. When sufficiently colonized, hepatocytes are lyzed and merozoites are released into the bloodstream, then start infection of erythrocytes (B″). This phase begins with merozoites invading RBCs (2’’) and transforming into trophozoites (3’’) then into schizonts (4’’), which infect other RBCs. At the end of this phase, trophozoites differentiate into male and female gametocytes (5’’), which are consumed by non-infected mosquitoes (7’’) The gametocytes that infect the female mosquitoes undergo several mutations in the digestive tract, before finally transforming into sporozoites that migrate to the mosquito’s salivary glands and are injected into man during the mosquito’s next blood meal. In this way, malaria spreads from person to person via the various mutations in humans and Anopheles mosquitoes. Illustration conceived with www.BioRender.com.

FIGURE 2

Illustrative structures of plant-based nanoparticles used to manage malaria. (A) Top: Plant extract-based metallic NPs coated with phytochemicals. Bottom: essential oil encapsulated in nanocapsule, both for the vector control. (B) Plant virus-based vaccine and antimalarial nanocarriers from mosaic viruses. (C) Nanocarriers encapsulating existing antimalarials or plant extract with antimalarial potential. Structures created with www.BioRender.com.

FIGURE 3

Illustrative microscopic appearance of biogenic nanoparticles with larvicidal properties. (A) Transmission Electron Micrograph (TEM) of biogenic gold NPs (AuNPs) from Cymbopogon citratus. (B) Scanning electron micrograph of biogenic silver NPs (AgNPs) from Eclipta prostate. (C) TEM of biogenic AgNPs from Solanum nigrum. (D) TEM of biogenic AuNPs from Artemisinin vulgaris. Reprinted from Murugan et al. (2015) (license number 5764290436824); Rajakumar and Abdul Rahuman (2011) (license number 5764290404752); Rawani et al. (2013) (license number 5764290360876) and Sundararajan and Ranjitha Kumari (2017) (license number 5764290220810) with the permission from Elsevier.

FIGURE 4

Illustration of nanoparticles targeting infected red blood cells and different features that can be used to decorate surface NPs to target passively or actively malaria biomarkers (A) and structures of chemical entities used as ligands targeting infected red blood cells (B). BioRender (online) and ChemSketch 2021.2.1 version C35E41 were used to create the structures in the two panels, respectively.

FIGURE 5

Schematic illustration of surface functional groups of mobile crystalline material 41 (MCM-41), 3-aminopropyl silane (aMCM-41), and 3-phenylpropyl silane (pMCM-41) cyclodextrin-based nanoformulations. Structures created with ChemSketch 2021.2.1 version C35E41.

FIGURE 6

Description of the interdisciplinarity connections between various disciplines enabling plant-based NPs development from the identification of plant materials to their application in nanotechnology for malaria management.