A Novel Near-infrared Responsive Lanthanide Upconversion Nanoplatform for Drug Delivery Based on Photocleavage of Cypate

Light-responsive drug delivery systems (DDS) exhibit the advantages of non-invasive, high controllability and spatio-temporal precision. However, DDS triggered by near-infrared (NIR) light are few and inefficient. In this work, we designed a novel NIR-responsive upconversion nanoplatform for drug delivery. In this nanoplatform, core-shell upconversion nanoparticle (UCNP) NaYF4:Yb,Er@NaYF4 was coated by mesoporous silica, and then successively coupled with NIR dye cypate, amantadine (AD) and beta-cyclodextrin (beta-CD) to block the pores and entrap the drugs. The cypate molecules with the feature of auto-sensitized photooxidation under 808 nm irradiation were, for the first time, employed as light-responsive moieties in DDS. The obtained nanoplatform was characterized by transmission electron microscopy (TEM), X-ray diffraction (XRD), N-2 adsorption/desorption, dynamic light scattering (DLS) and zeta potential analysis. Mechanism of photocleavage of cypate by singlet oxygen (O-1(2)) was also investigated by electron spin resonance (ESR) measurement. The nanoplatform loaded with antibiotic ofloxacin (OFL) showed a low drug leakage (6.9%) in the dark condition and a rapid release (50.9%) upon 808 nm irradiation with a relatively low power density of 0.5 W.cm(-2) for 40 min. Moreover, on-demand release of OFL can be achieved by adjusting the irradiation time (0 similar to 40 min). In vitro antibacterial experiments showed that the nanoplatform had a much better antibacterial effect against Staphylococcus aureus after 808 nm irradiation as compared with the group without irradiation. These results further verified the excellent NIR-responsive performance for the designed nanoplatform. In addition, the nanoplatform exhibited strong and stable upconversion luminescence (UCL) under 980 nm excitation, which can be applied for DDS tracing and bioimaging. The cytocompatibility of the nanoplatform was evaluated by methyl thiazolyl tetrazolium (MTT) assay, showing that the nanoplatform had no cytotoxic effect on human embryonic liver cell line (LO2) and exhibited great potentials in versatile bioapplications. Our work may open up a new avenue for the exploration of multi-functional NIR-responsive DDS.