Cellular uptake pathway and drug release characteristics of drug‐encapsulated glycol chitosan nanoparticles in live cells

Abstract

Herein, we evaluated the cellular uptake pathways of hydrophobically modified glycol chitosan (HGC) nanoparticles as nano-sized drug carriers using cellular imaging technology. The endocytic pathway of nanocarriers for intracellular drug delivery is of great interest for the design of high efficacy delivery carriers for therapeutic agents. To evaluate the cellular uptake pathways of HGC nanoparticles, HGC was chemically labeled with near infrared (NIR) fluorescence dye, Cy5.5, to visualize the nanoparticle under confocal laser scanning microscopy. The internalization pathways of HGC nanoparticles were evaluated after treatment of specific endocytosis inhibitors. Importantly, HCG nanoparticles showed different cellular uptake efficiency and intracellular fate in cytoplasm according to the internalization pathways. Furthermore, drug distribution also evaluated according to the endocytic pathways after treatment of drug encapsulated HGC nanoparticles. As a model drug, fluorescent photosensitizer, Ce6, was encapsulated into HGC (Ce6-HGC) nanoparticles and the distribution of Ce6 in cytoplasm was evaluated using confocal laser scanning microscopy. The intracellular drug distribution showed different manner through specific endocytic pathways. The cellular imaging technology is highly useful for evaluation of endocytosis pathways and intracellular fate of drug delivery carrier which are closely related to drug distribution and therapeutic efficacy.

Designer peptide delivery systems for gene therapy

“…Endocytosis is the primary mechanism for movement of extracellular material across biological membranes (11) .…”

“…If internalization is by endocytosis, as is predominantly the case, the objective is to escape the endosome, otherwise the genetic material will be degraded and expelled via a lysosome (11) . If endosomal escape is successful then the DNA must be delivered to the nucleus where it can finally exact a sustained therapeutic effect (12) .…”

Overviews on the cellular uptake mechanism of polysaccharide colloidal nanoparticles

“…The surface of nanoparticles is commonly coated with a layer of dissolved extracellular molecules in body fluids, such as proteins, sugars and lipids before their encounter with the cellular membranes, the so‐called protein corona . When reach the site of action, the loaded cargo may be released outside or cells take up nanoparticles and unload cargo at the desired intracellular compartment . Generally, the transport of macromolecular carriers such as nanoparticles from the cell surface to the lysosomal vesicles occurs with a process known as endocytosis .…”

The effect of mechanical properties of iron oxide nanoparticle-loaded functional nano-carrier on tumor targeting and imaging

“…It was also clearly observed that the accumulation of nano-particulates in tumor cells was higher than that in normal fibroblast cells, suggesting potentially more efficient tumor targeting. The enhanced cellular uptake of the chitosan-conjugated nano-carrier used as a vehicle of IONP might result from several endocytotic pathways, as previously reported [37,38]. Therefore, the result of an enhanced cellular uptake of IONP a b c d e by loading them into the nano-carrier supported the use of the IONP-loaded nano-carrier as an in-vivo MRI probe for tumor tissues.…”