Tiny Green Army: Fighting Malaria with Plants and Nanotechnology

Abstract

Malaria poses a global threat to human health, with millions of cases and thousands of deaths each year, mainly affecting developing countries in tropical and subtropical regions. Malaria's causative agent is Plasmodium species, generally transmitted in the hematophagous act of female Anopheles sp. mosquitoes. The main approaches to fighting malaria are eliminating the parasite through drug treatments and preventing transmission with vector control. However, vector and parasite resistance to current strategies set a challenge. In response to the loss of drug efficacy and the environmental impact of pesticides, the focus shifted to the search for biocompatible products that could be antimalarial. Plant derivatives have a millennial application in traditional medicine, including the treatment of malaria, and show toxic effects towards the parasite and the mosquito, aside from being accessible and affordable. Its disadvantage lies in the type of administration because green chemical compounds rapidly degrade. The nanoformulation of these compounds can improve bioavailability, solubility, and efficacy. Thus, the nanotechnology-based development of plant products represents a relevant tool in the fight against malaria. We aim to review the effects of nanoparticles synthesized with plant extracts on Anopheles and Plasmodium while outlining the nanotechnology green synthesis and current malaria prevention strategies.

Keywords: ACT; Anopheles; Plasmodium; green nanotechnology; plant extracts.

Figure 1

Schematic diagram for the biosynthesis of nanoparticles (NPs) via a green route using plant extract. A plant extract is a rich mixture of various metabolites and reductive biomolecules, each playing a pivotal role in the intricate process of reducing metal ions. Biomolecules stand out for their ability to transfer electrons to metallic ions, acting as potent reducing agents that instigate the ions’ reduction. The consequence of this reduction process is the development of structured patterns in the form of a crystalline formation known as a nucleus. The initiation of nucleation involves the aggregation of monomers in supersaturated systems. This crucial step establishes the foundation for the subsequent growth of these nuclei, leading to the formation of metal nanoparticles. As these atomic nuclei form, they provide a foundational platform for the reduced ions, facilitating their gradual deposition onto the surface. This deposition process significantly contributes to the enlargement of the particles. Biomolecules, in addition to their role as reducing agents, also serve as capping agents. They bind to the particle surface, acting as molecular guardians that effectively stabilize the size of the particles.

Figure 2

Action mechanisms of plant extracts and plant-derived nanoparticles. In the left panel, we summarize the phytochemicals’ effects. These molecules are recognized for their larvicidal and mosquitocidal properties, modulating the mosquito nervous system, by inducing either overstimulation or inhibition. This neuro-modulation results in observable behavioral changes, such as the reduced swimming and restless movement of larvae. In the right panel, effects of green nanoparticles (NPs) are illustrated. NPs with their optimal size effortlessly penetrate the membranes of mosquitos. Their mechanism of action involves interactions with DNA, contributing to enhanced apoptosis and oxidative stress within the target organisms. Notably, when deployed in field or semi-field conditions, these nanoparticles form an oily layer, a phenomenon correlated with a reduction in water oxygenation. Furthermore, both phytochemicals and green NPs influence factors such as the attraction of female mosquitoes to breeding sites, which are guided by olfactory cues susceptible to water quality. The effects of green-synthesized NPs may be due to the known effects of biomolecules present in plant extracts.

Figure 3

Effects of green-synthesized NPs on malaria prevention. NPs synthesized with plant extracts are toxic to early developmental stages of the malaria mosquito vector, Anopheles, acting against all four larvae stages (instar) and pupae, preventing the emergence of adult mosquitos capable of disease transmission. These nanoformulations also show adulticidal effects, impacting mosquito behavior and causing morphological damage. Furthermore, some studies showed that plant-extract NPs reduced the feeding of mosquitoes by preventing the biting habit. Oviposition is hindered in water treated with the nanoformulated plant extracts, thus reducing breeding site suitability. Green-synthesized NPs also improve the feeding activity of mosquito predators, lowering the survival chances of mosquito larvae and pupae. These formulations are eco-friendly because predators are not harmed. In addition, nanotechnology emphasizes the well-known antiparasitic activity of plant extracts. The antiplasmodial effects of plant-derived nanoformulations are parasitemia suppression by increased parasite mortality and metabolic impairment. Therefore, plant-derived nanoformulations are a potential tool to fight malaria.