Lung cell membrane-coated nanoparticles capable of enhanced internalization and translocation in pulmonary epithelial cells.

Cell membrane-coated nanoparticles (CMCNP), which involve coating a core nanoparticle (NP) with cell membranes, have been gaining attention due to their ability to mimic the properties of the cells, allowing for enhanced delivery and efficacy of therapeutics. Two CMCNP systems comprised of an acetalated dextran-based NP core loaded with curcumin (CUR) coated with cell membranes derived from pulmonary epithelial cells were developed. The NP were approximately 200 nm and their surface charges varied based on their coating, where CMCNP systems exhibited negative surface charge like natural cell membranes. The NP were smooth, spherical, and homogeneous with distinct coatings on their cores. Minimal in vitro toxicity was observed for the NP and controlled release of CUR was observed. The CMCNP internalized into and translocated across an in vitro pulmonary epithelial monolayer significantly more than the control NP. Blocking endocytosis pathways reduced the transcytosis of NP, indicating a relationship between endocytosis and transcytosis. These newly developed CMCNP have the potential to be used in pulmonary drug delivery applications to potentially enhance NP internalization and transport into and across the pulmonary epithelium.

Radiofrequency and Near-Infrared Responsive Core-Shell Nanostructures Using Layersome Templates for Cancer Treatment.

We report a multifunctional nanotherapeutic platform based on liposomes loaded with drug and iron oxide nanoparticles (IONs) coated with a gold nanoshell synthesized using a polyelectrolyte (layersome) soft templating technique. IONs and gold nanoshells were used to provide combined hyperthermia and triggered drug release via radio frequency (RF) or near-infrared (NIR) stimulation. IONs and the anticancer drug doxorubicin (DOX) were coencapsulated inside liposomes composed of zwitterionic phosphatidylcholine, anionic phosphatidylglycerol, and cholesterol lipids. Coating the magneto-liposomes with positively charged poly-l-lysine enriched the interface with gold anions to form a dense gold nanoshell and protected the structure against deformation and DOX cargo release during shell formation. After modification with thiol-terminated polyethylene glycol, intracellular delivery and release of DOX from the nanostructures was examined in A549 human lung cancer cells. The nanostructures retained their DOX cargo and remained in the cytosol after cellular uptake. Only when triggered by RF or NIR stimuli did the nanostructures release DOX, which then entered the cell nucleus. Compared to the single photothermal therapy or radio frequency treatment, the carriers with combined DOX and RF or NIR stimulation displayed higher therapeutic effect on A549 cells.