Limits...
Biodistribution and Toxicity Studies of PRINT Hydrogel Nanoparticles in Mosquito Larvae and Cells.

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

Bottom Line: Positively charged NPs were more associated with the gastric caeca in the gastrointestinal tract.Positively charged NPs trafficked to the cytosol, but negatively charged NPs co-localized with lysosomes.Following in vitro and in vivo challenge, none of the NPs tested induced any cytotoxic effects.

View Article: PubMed Central - PubMed

Affiliation: Department of Entomology, Iowa State University, Ames, Iowa, United States of America.

ABSTRACT
Mosquito-borne diseases continue to remain major threats to human and animal health and impediments to socioeconomic development. Increasing mosquito resistance to chemical insecticides is a great public health concern, and new strategies/technologies are necessary to develop the next-generation of vector control tools. We propose to develop a novel method for mosquito control that employs nanoparticles (NPs) as a platform for delivery of mosquitocidal dsRNA molecules to silence mosquito genes and cause vector lethality. Identifying optimal NP chemistry and morphology is imperative for efficient mosquitocide delivery. Toward this end, fluorescently labeled polyethylene glycol NPs of specific sizes, shapes (80 nm x 320 nm, 80 nm x 5000 nm, 200 nm x 200 nm, and 1000 nm x 1000 nm) and charges (negative and positive) were fabricated by Particle Replication in Non-Wetting Templates (PRINT) technology. Biodistribution, persistence, and toxicity of PRINT NPs were evaluated in vitro in mosquito cell culture and in vivo in Anopheles gambiae larvae following parenteral and oral challenge. Following parenteral challenge, the biodistribution of the positively and negatively charged NPs of each size and shape was similar; intense fluorescence was observed in thoracic and abdominal regions of the larval body. Positively charged NPs were more associated with the gastric caeca in the gastrointestinal tract. Negatively charged NPs persisted through metamorphosis and were observed in head, body and ovaries of adults. Following oral challenge, NPs were detected in the larval mid- and hindgut. Positively charged NPs were more efficiently internalized in vitro than negatively charged NPs. Positively charged NPs trafficked to the cytosol, but negatively charged NPs co-localized with lysosomes. Following in vitro and in vivo challenge, none of the NPs tested induced any cytotoxic effects.

No MeSH data available.


Related in: MedlinePlus

Survivorship of An. gambiae larvae after injection with particles.Fourth instar larvae were injected with 45 nL (235 ng) (A) 80 nm x 320 nm (B) 200 nm x 200 nm and (C) 80 nm x 5000 nm particles. Larval survival was monitored through 144 h post-injection. Data are expressed as the mean ± SEM of five independent experiments. No statistical difference between groups was observed at p<0.05.
© Copyright Policy
Related In: Results  -  Collection

License
getmorefigures.php?uid=PMC4440723&req=5

pntd.0003735.g007: Survivorship of An. gambiae larvae after injection with particles.Fourth instar larvae were injected with 45 nL (235 ng) (A) 80 nm x 320 nm (B) 200 nm x 200 nm and (C) 80 nm x 5000 nm particles. Larval survival was monitored through 144 h post-injection. Data are expressed as the mean ± SEM of five independent experiments. No statistical difference between groups was observed at p<0.05.

Mentions: Complementing the in vitro cell viability studies, in vivo studies were conducted to determine if the NPs caused untoward effects in An. gambiae larvae. Fourth instar larvae were intrathoracically injected with NPs and their survival monitored for 6 days p.i., Larvae injected with water were used as controls. No significant mortality was observed by any of the NP groups studied compared to controls (Fig 7). The low levels of mortality observed in larvae injected with water are likely caused by the stress of injection. Together, these data show that PRINT NPs themselves do not induce any untoward effects in An. gambiae larvae.


Biodistribution and Toxicity Studies of PRINT Hydrogel Nanoparticles in Mosquito Larvae and Cells.

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

Survivorship of An. gambiae larvae after injection with particles.Fourth instar larvae were injected with 45 nL (235 ng) (A) 80 nm x 320 nm (B) 200 nm x 200 nm and (C) 80 nm x 5000 nm particles. Larval survival was monitored through 144 h post-injection. Data are expressed as the mean ± SEM of five independent experiments. No statistical difference between groups was observed at p<0.05.
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4440723&req=5

pntd.0003735.g007: Survivorship of An. gambiae larvae after injection with particles.Fourth instar larvae were injected with 45 nL (235 ng) (A) 80 nm x 320 nm (B) 200 nm x 200 nm and (C) 80 nm x 5000 nm particles. Larval survival was monitored through 144 h post-injection. Data are expressed as the mean ± SEM of five independent experiments. No statistical difference between groups was observed at p<0.05.
Mentions: Complementing the in vitro cell viability studies, in vivo studies were conducted to determine if the NPs caused untoward effects in An. gambiae larvae. Fourth instar larvae were intrathoracically injected with NPs and their survival monitored for 6 days p.i., Larvae injected with water were used as controls. No significant mortality was observed by any of the NP groups studied compared to controls (Fig 7). The low levels of mortality observed in larvae injected with water are likely caused by the stress of injection. Together, these data show that PRINT NPs themselves do not induce any untoward effects in An. gambiae larvae.

Bottom Line: Positively charged NPs were more associated with the gastric caeca in the gastrointestinal tract.Positively charged NPs trafficked to the cytosol, but negatively charged NPs co-localized with lysosomes.Following in vitro and in vivo challenge, none of the NPs tested induced any cytotoxic effects.

View Article: PubMed Central - PubMed

Affiliation: Department of Entomology, Iowa State University, Ames, Iowa, United States of America.

ABSTRACT
Mosquito-borne diseases continue to remain major threats to human and animal health and impediments to socioeconomic development. Increasing mosquito resistance to chemical insecticides is a great public health concern, and new strategies/technologies are necessary to develop the next-generation of vector control tools. We propose to develop a novel method for mosquito control that employs nanoparticles (NPs) as a platform for delivery of mosquitocidal dsRNA molecules to silence mosquito genes and cause vector lethality. Identifying optimal NP chemistry and morphology is imperative for efficient mosquitocide delivery. Toward this end, fluorescently labeled polyethylene glycol NPs of specific sizes, shapes (80 nm x 320 nm, 80 nm x 5000 nm, 200 nm x 200 nm, and 1000 nm x 1000 nm) and charges (negative and positive) were fabricated by Particle Replication in Non-Wetting Templates (PRINT) technology. Biodistribution, persistence, and toxicity of PRINT NPs were evaluated in vitro in mosquito cell culture and in vivo in Anopheles gambiae larvae following parenteral and oral challenge. Following parenteral challenge, the biodistribution of the positively and negatively charged NPs of each size and shape was similar; intense fluorescence was observed in thoracic and abdominal regions of the larval body. Positively charged NPs were more associated with the gastric caeca in the gastrointestinal tract. Negatively charged NPs persisted through metamorphosis and were observed in head, body and ovaries of adults. Following oral challenge, NPs were detected in the larval mid- and hindgut. Positively charged NPs were more efficiently internalized in vitro than negatively charged NPs. Positively charged NPs trafficked to the cytosol, but negatively charged NPs co-localized with lysosomes. Following in vitro and in vivo challenge, none of the NPs tested induced any cytotoxic effects.

No MeSH data available.


Related in: MedlinePlus