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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 1 and 3 day(s) oral challenges.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 1 day (A) and 3 day (C) oral challenge (250 μg/mL). 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 following 1 day (B) and 3 day (D) oral challenge. In mosquitoes challenged for 1 d, tissue tropisms and fluorescence intensity decreased substantially by 1 or 2 d post challenge. However, some organs/tissues still contained fluorescence signal at 7 d post challenge. In mosquitoes challenged for 3 d, tissue tropisms and fluorescence intensity were greater and of longer duration than in mosquitoes challenged for only 1 d. VD = ventral diverticulum; DD = dorsal diverticula; FG = foregut; MG = midgut; HG = hindgut; MT = Malpighian tubules; TM = thoracic muscles.
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pntd.0003745.g007: Tissue tropisms and fluorescence intensity of positively and negatively charged 80 nm x 320 nm hydrogel nanoparticles in Anopheles gambiae females following 1 and 3 day(s) oral challenges.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 1 day (A) and 3 day (C) oral challenge (250 μg/mL). 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 following 1 day (B) and 3 day (D) oral challenge. In mosquitoes challenged for 1 d, tissue tropisms and fluorescence intensity decreased substantially by 1 or 2 d post challenge. However, some organs/tissues still contained fluorescence signal at 7 d post challenge. In mosquitoes challenged for 3 d, tissue tropisms and fluorescence intensity were greater and of longer duration than in mosquitoes challenged for only 1 d. VD = ventral diverticulum; DD = dorsal diverticula; FG = foregut; MG = midgut; HG = hindgut; MT = Malpighian tubules; TM = thoracic muscles.

Mentions: To better understand the biodistribution of NPs at the organ and cellular levels over time, 1 d oral challenges were conducted with the respective NPs (Fig 1). Mosquitoes were dissected (Fig 2) and examined using fluorescence microscopy to determine tissue tropisms and the duration of the tropisms (Fig 7A), and the intensity of the NP fluorescent signal overtime (Fig 7B). All NPs exhibited similar alimentary tract tropisms (Fig 8). Following oral challenge with the 250 μg/mL NPs, both positively and negatively charged NPs were detected abundantly in dorsal and ventral diverticula, cardia/foregut, and midgut (Fig 8). Interestingly, large accumulations of both positively and negatively charged NPs were consistently detected at 1 d post challenge in the cardia and foregut (Fig 8), organs which contain the first likely target cells in the alimentary tract that the NPs would encounter following ingestion. The tissue tropisms and intensity of fluorescence were similar for the different NPs. For example, when orally challenged with the 250 μg/mL dose of 80 nm x 320 nm positively and negatively charged NPs, tissue tropisms were greatest on days 1 and 2 post ingestion (Fig 7A). Tissue tropisms and fluorescent intensity then typically declined in organs (confirming the whole body imaging results), and NPs were only detectable in some tissues at low intensity at 7 d post ingestion (Fig 7A and 7B). When the mosquitoes were orally challenged with the 50 μg/mL dose of positively charged 80 nm x 320 nm NPs, tissue tropisms were similar to but of shorter duration (S1A Fig) than in mosquitoes challenged with the 250 μg/mL dose of NPs (Fig 7A). In addition, the fluorescent signal was less intense in mosquitoes challenged with the lower dose of NPs (S1B Fig) than in the mosquitoes challenged with the higher dose of NPs (Fig 7B). The differences in tissue tropisms and fluorescent intensities were not as pronounced when mosquitoes were orally challenged with 250 or 50 μg/mL of negatively charged 80 nm x 320 nm NPs (Figs 7A, 7B, S1A and S1B).


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 1 and 3 day(s) oral challenges.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 1 day (A) and 3 day (C) oral challenge (250 μg/mL). 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 following 1 day (B) and 3 day (D) oral challenge. In mosquitoes challenged for 1 d, tissue tropisms and fluorescence intensity decreased substantially by 1 or 2 d post challenge. However, some organs/tissues still contained fluorescence signal at 7 d post challenge. In mosquitoes challenged for 3 d, tissue tropisms and fluorescence intensity were greater and of longer duration than in mosquitoes challenged for only 1 d. VD = ventral diverticulum; DD = dorsal diverticula; FG = foregut; MG = midgut; HG = hindgut; MT = Malpighian tubules; TM = thoracic muscles.
© Copyright Policy
Related In: Results  -  Collection

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

pntd.0003745.g007: Tissue tropisms and fluorescence intensity of positively and negatively charged 80 nm x 320 nm hydrogel nanoparticles in Anopheles gambiae females following 1 and 3 day(s) oral challenges.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 1 day (A) and 3 day (C) oral challenge (250 μg/mL). 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 following 1 day (B) and 3 day (D) oral challenge. In mosquitoes challenged for 1 d, tissue tropisms and fluorescence intensity decreased substantially by 1 or 2 d post challenge. However, some organs/tissues still contained fluorescence signal at 7 d post challenge. In mosquitoes challenged for 3 d, tissue tropisms and fluorescence intensity were greater and of longer duration than in mosquitoes challenged for only 1 d. VD = ventral diverticulum; DD = dorsal diverticula; FG = foregut; MG = midgut; HG = hindgut; MT = Malpighian tubules; TM = thoracic muscles.
Mentions: To better understand the biodistribution of NPs at the organ and cellular levels over time, 1 d oral challenges were conducted with the respective NPs (Fig 1). Mosquitoes were dissected (Fig 2) and examined using fluorescence microscopy to determine tissue tropisms and the duration of the tropisms (Fig 7A), and the intensity of the NP fluorescent signal overtime (Fig 7B). All NPs exhibited similar alimentary tract tropisms (Fig 8). Following oral challenge with the 250 μg/mL NPs, both positively and negatively charged NPs were detected abundantly in dorsal and ventral diverticula, cardia/foregut, and midgut (Fig 8). Interestingly, large accumulations of both positively and negatively charged NPs were consistently detected at 1 d post challenge in the cardia and foregut (Fig 8), organs which contain the first likely target cells in the alimentary tract that the NPs would encounter following ingestion. The tissue tropisms and intensity of fluorescence were similar for the different NPs. For example, when orally challenged with the 250 μg/mL dose of 80 nm x 320 nm positively and negatively charged NPs, tissue tropisms were greatest on days 1 and 2 post ingestion (Fig 7A). Tissue tropisms and fluorescent intensity then typically declined in organs (confirming the whole body imaging results), and NPs were only detectable in some tissues at low intensity at 7 d post ingestion (Fig 7A and 7B). When the mosquitoes were orally challenged with the 50 μg/mL dose of positively charged 80 nm x 320 nm NPs, tissue tropisms were similar to but of shorter duration (S1A Fig) than in mosquitoes challenged with the 250 μg/mL dose of NPs (Fig 7A). In addition, the fluorescent signal was less intense in mosquitoes challenged with the lower dose of NPs (S1B Fig) than in the mosquitoes challenged with the higher dose of NPs (Fig 7B). The differences in tissue tropisms and fluorescent intensities were not as pronounced when mosquitoes were orally challenged with 250 or 50 μg/mL of negatively charged 80 nm x 320 nm NPs (Figs 7A, 7B, S1A and S1B).

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