Silencing genes in
insects by introducing double-stranded RNA (dsRNA)
in the diet holds promise as a new pest management method. It has
been demonstrated that nanoparticles (NPs) can potentiate dsRNA silencing
effects by promoting cellular internalization and protecting dsRNA
against early degradation. However, many mysteries of how NPs and
dsRNA are internalized by gut epithelial cells and, subsequently,
transported across the midgut epithelium remain to be unraveled. The
sole purpose of the current study is to investigate the role of endocytosis
and transcytosis in the transport of branched amphipathic peptide
nanocapsules (BAPCs) associated with dsRNA through midgut epithelium
cells.
Spodoptera frugiperda
midguts
and the epithelial cell line Sf9, derived from
S. frugiperda
, were used to study transcytosis and endocytosis, respectively.
Results suggest that clathrin-mediated endocytosis and macropinocytosis
are largely responsible for cellular uptake, and once within the midgut,
transcytosis is involved in shuttling BAPCs–dsRNA from the
lumen to the hemolymph. In addition, BAPCs were not found to be toxic
to Sf9 cells or generate damaging reactive species once internalized.
Fungal
infections are becoming a global health problem. A major
limiting factor for the development of antifungals is the high impermeability
of the rigid and thick fungal cell wall. Compared to mammalian cells,
fungal cells are more resilient to perforation due to the presence
of this carbohydrate armor. While a few methods have been reported
to penetrate the fungal cell wall, such as electroporation, biolistics,
glass beads, and the use of monovalent cations, such methods are generally
time-consuming, compromise cell viability, and often lead to low permeation
rates. In addition, their use remains limited to in vitro applications due to the collateral damage that these techniques
could cause to healthy living tissues. Presented in this study is
a delivery approach based on the generation of transient breaks, or
pores, in the cell wall. Breaks are generated by cavitation and shock
waves resulting from the irradiation of gold nanoparticles with a
femtosecond infrared laser. Such an approach enabled the delivery
of membrane impermeable molecules (i.e., calcein and plasmid DNA)
into Saccharomyces cerevisiae, a fungal
model organism. This method is expected to exhibit high biocompatibility
and holds potential for clinical applications for the treatment of
fungal infections given that neither the laser irradiation nor the
nanoparticles have been found to damage cells. Mechanistical aspects
of photoporation, such as the proximity needed between the nanoparticle
and the cell membrane for these processes to take place, are also
discussed. Hence, the laser-assisted drug delivery approach described
here is suitable for further preclinical evaluation in oral, vaginal,
and skin mycoses where current treatments are insufficient due to
host-related adverse reactions, poor fungal cell penetration, or risk
of developing antifungal resistance.
Nanoparticles (NPs) have been shown to be a suitable mRNA delivery platform by conferring protection against ribonucleases and facilitating cellular uptake. Several NPs have succeeded in delivering mRNA intranasally, intratracheally,...
The back cover image is based on the Review Article Prospects, challenges and current status of RNAi through insect feeding by Luz‐Adriana Avila et al., https://doi.org/https://doi.org/10.1002/ps.5588.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.