Biodistribution and Trafficking of Hydrogel Nanoparticles in Adult Mosquitoes

Abstract

BackgroundNanotechnology offers great potential for molecular genetic investigations and potential control of medically important arthropods. Major advances have been made in mammalian systems to define nanoparticle (NP) characteristics that condition trafficking and biodistribution of NPs in the host. Such information is critical for effective delivery of therapeutics and molecules to cells and organs, but little is known about biodistribution of NPs in mosquitoes.Methodology/Principal FindingsPRINT technology was used to construct a library of fluorescently labeled hydrogel NPs of defined size, shape, and surface charge. The biodistribution (organ, tissue, and cell tropisms and trafficking kinetics) of positively and negatively charged 200 nm x 200 nm, 80 nm x 320 nm, and 80 nm x 5000 nm NPs was determined in adult Anopheles gambiae mosquitoes as a function of the route of challenge (ingestion, injection or contact) using whole body imaging and fluorescence microscopy. Mosquitoes readily ingested NPs in sugar solution. Whole body fluorescence imaging revealed substantial NP accumulation (load) in the alimentary tracts of the adult mosquitoes, with the greatest loads in the diverticula, cardia and foregut. Positively and negatively charged NPs differed in their biodistribution and trafficking. Following oral challenge, negatively charged NPs transited the alimentary tract more rapidly than positively charged NPs. Following contact challenge, negatively charged NPs trafficked more efficiently in alimentary tract tissues. Following parenteral challenge, positively and negatively charged NPs differed in tissue tropisms and trafficking in the hemocoel. Injected NPs were also detected in cardia/foregut, suggesting trafficking of NPs from the hemocoel into the alimentary tract.Conclusions/SignificanceHerein we have developed a tool box of NPs with the biodistribution and tissue tropism characteristics for gene structure/function studies and for delivery of vector lethal cargoes for mosquito control.

RNA Interference for Mosquito and Mosquito-Borne Disease Control

“…We contend that RNAi could be adapted and implemented using the framework for existing vector control tools, including larvicides, contact and residual sprays, toxic baits, and LLINs. To translate RNAi to field applicability, RNAi triggers likely will need to be combined with biotic (e.g., a virus, yeast or bacterial expression system) or abiotic (e.g., nanoparticle) systems that mediate both protection and uptake of the RNAi trigger [13,27,46,47,48,49,50,51]. An RNAi approach to mosquito control offers a number of advantages over traditional chemical pesticides, including vastly improved species-specificity with diminished environmental toxicity compared with chemical pesticides.…”

“…The composition of nanoparticles varies greatly from biomacromolecular material like chitosan or peptides to chemically produced liposomes and polyethylene glycol (PEG) [49,50,72,157]. Biomacromolecular nanoparticles are advantageous as they will be degraded rather than accumulating in the environment.…”

“…Uptake and bio-distribution without toxicity have been demonstrated in larval and adult An. gambiae [50,51]. …”

“…By the same logic, mosquitocidal RNAi triggers could be applied to target essential genes for embryogenesis in Attractive Baited Oviposition Traps (ABOTs) [43,44,45]. In both baited strategies and more traditional insecticidal delivery approaches (ultra-low volume or residual sprays, or LLINs), RNAi triggers may be more efficacious in combination with biotic (e.g., a virus, yeast or bacterial expression system) or abiotic (e.g., nanoparticle) systems that mediate both protection and uptake of RNAi triggers [13,27,46,47,48,49,50,51]. …”

Nano-enabled delivery of diverse payloads across complex biological barriers

“…Polyethylene glycol nanoparticles of various shapes, sizes, and charge exhibited different biodistribution and persistence profiles when administered to mosquito larvae and adults [147, 149]. Typically, negatively particles had a higher in vivo persistence compared to positively charged particles except for long, rod-shaped particles where no difference was observed.…”