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.
Core/shell gold "raspberry" nanostructures capable of multiple therapeutic functionalities were synthesized using a template composed of monodispersed anionic protein (bovine serum albumin) nanoparticles coated with a cationic biopolymer (poly-L-lysine). The nanostructures exhibited high photothermal conversion efficiency when exposed to a near-infrared (NIR) laser, which led to significant cellular inhibition of A549 human lung cancer cells due to intracellular hyperthermia. The raspberry structures also provided hot spots for surface-enhanced Raman scattering (SERS) ratiometric sensing of intracellular reactive oxygen species (ROS) when modified with the Raman reporter molecule 4-aminothiophenol (4-ATP). ROS was detected in A549 lung cancer cells upon photothermal heating of internalized nanostructures, enabling a possible mechanism for feedback on therapeutic efficacy. This was confirmed by adding the antioxidant N-acetylcysteine (NAC) and using a complementary fluorescence technique, which showed that the amount of detectable intracellular ROS decreased. These safe-by-design gold raspberry nanostructures could be promising for simultaneous therapeutic applications and monitoring therapeutic efficacy.
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.