Tailoring the interface between hybrid nanostructures and cells for stimuli-based theranostic systems
Abstract
A nanostructure-based theranostic system offers a promising approach by integrating therapeutic and diagnostic functions into a single platform. However, significant challenges remain with these nanomaterials when used as theranostic systems, including (1) poor biocompatibility, (2) unsatisfied delivery outcome to targeted sites due to endothelial barriers such as the endothelial barrier and an uncontrollable drug release profile, and (3) low sensing performance. Therefore, this research aims to develop multifunctional nanostructures with unique physical and chemical properties and suitable surface modifications for enhanced barrier transportation, stimuli-responsive drug release and improved sensing performance for theranostic systems. First, the core shell upconversion nanoparticles (UCNPs) modified with cationic biopolymer, N, N, N-trimethyl chitosan (TMC), were developed and applied to overcome endothelial barriers. The results indicate that the transport percentage of the UCNPs@SiO2 with the surface modification of TMC through the in vitro endothelial barrier is twice higher than the one without TMC. Due to the efficient transport behavior, TMC has further been studied to develop a new nanosphere to facilitate the transport of hydrophobic drugs, curcumin, to across endothelial barriers efficiently. The results reveal that TMC nanospheres significantly extend the release of curcumin over a 72-hour period, with curcumin transport across the endothelial barrier being 26.7% greater than that of the untreated system, indicating improved barrier permeability. In addition, a hybrid TMC-based magnetic nano-system was designed to further control the drug releasing while efficiently crossing the tissue barrier. The results show that the hybrid magnetic nano-system releases 50% more curcumin under AMF exposure for six hours compared to the non-exposed system, and numerous openings appear at the paracellular tight junction sites, suggesting effective stimuli-responsive drug release and improved barrier transport. Finally, CdSe/ZnS quantum dots (QDs)-based Förster resonance energy transfer (FRET) sensor was continuously developed for quickly detecting human tear glucose for the non-invasive diagnosis of diabetes. It shows high selectivity to glucose and good sensitivity at the range of 0.01-1 mM, with a limit of detection of 0.01 mM. In summary, suitable surface modification of nanostructures with special optical and magnetic properties is critical to overcoming the limitations of theranostic systems.