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Biodistribution and trafficking of hydrogel nanoparticles in adult mosquitoes.

Paquette CC, Phanse Y, Perry JL, Sanchez-Vargas I, Airs PM, Dunphy BM, Xu J, Carlson JO, Luft JC, DeSimone JM, Bartholomay LC, Beaty BJ - PLoS Negl Trop Dis (2015)

Bottom Line: 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.Injected NPs were also detected in cardia/foregut, suggesting trafficking of NPs from the hemocoel into the alimentary tract.Herein 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.

View Article: PubMed Central - PubMed

Affiliation: Department of Microbiology, Immunology, and Pathology, Colorado State University, Fort Collins, Colorado, United States of America.

ABSTRACT

Background: Nanotechnology 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 findings: PRINT 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/significance: Herein 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.

No MeSH data available.


Related in: MedlinePlus

Tissue tropisms and fluorescence intensity of positively and negatively charged 80 nm x 320 nm hydrogel nanoparticles in Anopheles gambiae females following parenteral challenge.(A) Tissue tropisms (percent of mosquitoes with NP fluorescent signal of any intensity detected in the respective organ or tissue) of positively and negatively charged 80 x 320nm NPs in An. gambiae following parenteral challenge (250 μg/ml). (B) Fluorescence intensity (mean level of fluorescence intensity (NP load) in organs and tissues containing NPs) of positively and negatively charged 80 x 320 nm NPs in An. gambiae organs and tissues following parenteral challenge. NP tissue tropisms and loads were greater and of longer duration in most tissues females injected with positively charged NPs than in those injected with negatively charged NPs. Negatively charged NPs were most frequently associated with head and proboscis tissues. VD = ventral diverticulum; DD = dorsal diverticula; FG = foregut; MG = midgut; HG = hindgut; MT = Malpighian tubules; TM = thoracic muscle.
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pntd.0003745.g011: Tissue tropisms and fluorescence intensity of positively and negatively charged 80 nm x 320 nm hydrogel nanoparticles in Anopheles gambiae females following parenteral challenge.(A) Tissue tropisms (percent of mosquitoes with NP fluorescent signal of any intensity detected in the respective organ or tissue) of positively and negatively charged 80 x 320nm NPs in An. gambiae following parenteral challenge (250 μg/ml). (B) Fluorescence intensity (mean level of fluorescence intensity (NP load) in organs and tissues containing NPs) of positively and negatively charged 80 x 320 nm NPs in An. gambiae organs and tissues following parenteral challenge. NP tissue tropisms and loads were greater and of longer duration in most tissues females injected with positively charged NPs than in those injected with negatively charged NPs. Negatively charged NPs were most frequently associated with head and proboscis tissues. VD = ventral diverticulum; DD = dorsal diverticula; FG = foregut; MG = midgut; HG = hindgut; MT = Malpighian tubules; TM = thoracic muscle.

Mentions: At 1 and 2 d post injection, positively charged NPs were detected in more alimentary tract organs and tissues and at greater intensity than negatively charged NPs (Fig 11). Negatively charged NPs were more associated with head and proboscis tissues (Fig 11A). NPs were detected consistently in and/or associated with multiple organs and cells, including trachea (Fig 12A), muscle and nerves on the surface of organs such as midgut and ventral diverticulum and Malpighian tubules (Fig 12A), and less frequently in hemocytes, head, proboscis, and thoracic muscles. Positively charged NPs were detected in Malpighian tubules in 100% of mosquitoes following parenteral challenge (Figs 11A and 12A), but not in Malpighian tubules following oral challenge (Fig 7A). This suggests that Malpighian tubules take up particles from the hemolymph but not from the alimentary tract. Negatively charged NPs were very infrequently detected in Malpighian tubules following oral challenge (Fig 7A), and not detected following parenteral challenge (Figs 7A and 11A). Negatively charged NPs were frequently detected abundantly in tissues of the proboscis and head, a similar biodistribution to that demonstrated for negatively charged NPs following 3 d ad libitum challenge (Fig 10B). In general, following injection, negatively charged NPs were more associated with punctate fluorescence, and positively charged NPs were more associated with the basal lamina of multiple organs (Fig 12B) Following injection, positively charged NPs persisted in organs and tissues longer or were more stable (detectable over time) than negatively charged NPs (Fig 11). Negatively charged NPs are probably not internalized by the cells in tissues and organs and released with the hemolymph upon dissection (see Fig 1 in companion paper [38]).


Biodistribution and trafficking of hydrogel nanoparticles in adult mosquitoes.

Paquette CC, Phanse Y, Perry JL, Sanchez-Vargas I, Airs PM, Dunphy BM, Xu J, Carlson JO, Luft JC, DeSimone JM, Bartholomay LC, Beaty BJ - PLoS Negl Trop Dis (2015)

Tissue tropisms and fluorescence intensity of positively and negatively charged 80 nm x 320 nm hydrogel nanoparticles in Anopheles gambiae females following parenteral challenge.(A) Tissue tropisms (percent of mosquitoes with NP fluorescent signal of any intensity detected in the respective organ or tissue) of positively and negatively charged 80 x 320nm NPs in An. gambiae following parenteral challenge (250 μg/ml). (B) Fluorescence intensity (mean level of fluorescence intensity (NP load) in organs and tissues containing NPs) of positively and negatively charged 80 x 320 nm NPs in An. gambiae organs and tissues following parenteral challenge. NP tissue tropisms and loads were greater and of longer duration in most tissues females injected with positively charged NPs than in those injected with negatively charged NPs. Negatively charged NPs were most frequently associated with head and proboscis tissues. VD = ventral diverticulum; DD = dorsal diverticula; FG = foregut; MG = midgut; HG = hindgut; MT = Malpighian tubules; TM = thoracic muscle.
© Copyright Policy
Related In: Results  -  Collection

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Show All Figures
getmorefigures.php?uid=PMC4440717&req=5

pntd.0003745.g011: Tissue tropisms and fluorescence intensity of positively and negatively charged 80 nm x 320 nm hydrogel nanoparticles in Anopheles gambiae females following parenteral challenge.(A) Tissue tropisms (percent of mosquitoes with NP fluorescent signal of any intensity detected in the respective organ or tissue) of positively and negatively charged 80 x 320nm NPs in An. gambiae following parenteral challenge (250 μg/ml). (B) Fluorescence intensity (mean level of fluorescence intensity (NP load) in organs and tissues containing NPs) of positively and negatively charged 80 x 320 nm NPs in An. gambiae organs and tissues following parenteral challenge. NP tissue tropisms and loads were greater and of longer duration in most tissues females injected with positively charged NPs than in those injected with negatively charged NPs. Negatively charged NPs were most frequently associated with head and proboscis tissues. VD = ventral diverticulum; DD = dorsal diverticula; FG = foregut; MG = midgut; HG = hindgut; MT = Malpighian tubules; TM = thoracic muscle.
Mentions: At 1 and 2 d post injection, positively charged NPs were detected in more alimentary tract organs and tissues and at greater intensity than negatively charged NPs (Fig 11). Negatively charged NPs were more associated with head and proboscis tissues (Fig 11A). NPs were detected consistently in and/or associated with multiple organs and cells, including trachea (Fig 12A), muscle and nerves on the surface of organs such as midgut and ventral diverticulum and Malpighian tubules (Fig 12A), and less frequently in hemocytes, head, proboscis, and thoracic muscles. Positively charged NPs were detected in Malpighian tubules in 100% of mosquitoes following parenteral challenge (Figs 11A and 12A), but not in Malpighian tubules following oral challenge (Fig 7A). This suggests that Malpighian tubules take up particles from the hemolymph but not from the alimentary tract. Negatively charged NPs were very infrequently detected in Malpighian tubules following oral challenge (Fig 7A), and not detected following parenteral challenge (Figs 7A and 11A). Negatively charged NPs were frequently detected abundantly in tissues of the proboscis and head, a similar biodistribution to that demonstrated for negatively charged NPs following 3 d ad libitum challenge (Fig 10B). In general, following injection, negatively charged NPs were more associated with punctate fluorescence, and positively charged NPs were more associated with the basal lamina of multiple organs (Fig 12B) Following injection, positively charged NPs persisted in organs and tissues longer or were more stable (detectable over time) than negatively charged NPs (Fig 11). Negatively charged NPs are probably not internalized by the cells in tissues and organs and released with the hemolymph upon dissection (see Fig 1 in companion paper [38]).

Bottom Line: 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.Injected NPs were also detected in cardia/foregut, suggesting trafficking of NPs from the hemocoel into the alimentary tract.Herein 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.

View Article: PubMed Central - PubMed

Affiliation: Department of Microbiology, Immunology, and Pathology, Colorado State University, Fort Collins, Colorado, United States of America.

ABSTRACT

Background: Nanotechnology 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 findings: PRINT 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/significance: Herein 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.

No MeSH data available.


Related in: MedlinePlus