Enhanced endosomal escape of siRNA-incorporating hybrid nanoparticles from calcium phosphate and PEG-block charge-conversional polymer for efficient gene knockdown with negligible cytotoxicity

Endocytosis of Particle Formulations by Macrophages and Its Application to Clinical Treatment

“…To overcome these problems, nanoparticles will be effective, because they are able to escape from endosomes into the cytosol, where these nanoparticles release drugs. Based on this strategy, delivery of siRNA-containing nanoparticles into HeLa cells and human pancreatic carcinoma PanC-1 cells is reported to be successful [69,70].…”

Technologies for Investigating the Physiological Barriers to Efficient Lipid Nanoparticle–siRNA Delivery

“…The drawbacks are low throughput, inability to detect metabolites, and difficulty in achieving precise quantification of fluorescence intensity on IF-stained tissue sections. There are examples of applying such histological methods to investigate siRNA deposition in the liver (Shi et al 2011), tumor (Yoshizawa et al 2008;Mikhaylova et al 2009), lung (Tayyari et al 2011), or even subcellular compartments (Akita et al 2010;Basha et al 2011;Pittella et al 2011). …”

“…Others (Akita et al 2010;Pittella et al 2011) have applied confocal microscopy where they labeled siRNA with Cy5 (red) and stained siRNA-treated cells with LysoTracker (green), and they calculated the ratio of yellow pixels (co-localization of siRNA with LysoTracker), which was equal to yellow pixels divided by the sum of yellow and red pixels. If more yellow perinuclear signals were observed and the yellow co-localization ratio was higher, it indicated more endosomal/lysosomal captured siRNAs.…”

Effects of major parameters of nanoparticles on their physical and chemical properties and recent application of nanodrug delivery system in targeted chemotherapy

“…The charge response between particles and cells is an important basis for these biological performances. 54 The experimental results of Tang et al showed that when the nanoparticles are dispersed in the culture medium, only positively charged particles can be ingested by the cells; if the particles are connected to the protein, the electrostatic difference between the positively and negatively charged particles can be almost completely eliminated. 55 Although protein-coated particles may help identify antigens or receptors, they are not very important in determining particle-to-cell attraction.…”