In recent decades, the excellent properties of rare-earth doped nanoparticles (RENPs), such as multiple optical properties, high photostability, long lifetime, and low cytotoxicity, have made them... Show moreIn recent decades, the excellent properties of rare-earth doped nanoparticles (RENPs), such as multiple optical properties, high photostability, long lifetime, and low cytotoxicity, have made them one of the main research trends for optical probes. Their promising applications in the biomedical field have further contributed to this trend.This thesis focuses on two aspects of RENPs as biological carriers and multifunctional imaging probes for disease therapy and diagnosis. Firstly, we investigated the effectiveness of a nanoplatform constructed with upconversion nanoparticles (UCNPs) as a carrier for immunotherapy due to the modifiability and high luminescence efficiency of UCNPs. This approach successfully achieved an immunotherapeutic strategy that could be tracked in real time.Secondly, as single imaging modality probes are time-consuming and have low diagnostic efficiency in disease diagnosis, we synthesized and optimized RENPs with multifunctional imaging capabilities using specific ions in their compositions, and we also performed preliminary evaluations of various imaging properties. Our findings provide a viable idea for reducing healthcare costs and improving healthcare efficiency. Show less
Kv11.1-induced cardiotoxicity has emerged as an unanticipated adverse effect of many pharmacological agents and has become a major obstacle in drug development over the past decades. In this thesis... Show moreKv11.1-induced cardiotoxicity has emerged as an unanticipated adverse effect of many pharmacological agents and has become a major obstacle in drug development over the past decades. In this thesis, allosteric modulation of the Kv11.1 channel has been extensively explored, and negative allosteric modulators were shown to relieve the proarrhythmic effects of structurally and therapeutically diverse Kv11.1 blockers. The most potent modulators may be developed as a new class of antiarrhythmic medications in the future. On the other hand, kinetic binding parameters of a wide range of Kv11.1 blockers at the channel have been thoroughly investigated in this thesis. Association and dissociation rates or residence times are strongly suggested to be integrated with equilibrium affinity values into the future paradigms for a better and more comprehensive evaluation of Kv11.1 liability of drug candidates. The __kon-koff-KD__ kinetic map provides a first and promising classification of Kv11.1 blockers, which could be beneficial and indicative for drug researchers to design compounds with less Kv11.1-mediated cardiac side effects in the early stage of drug development. Hopefully, all findings in this thesis have brought new insights into Kv11.1-induced cardiac arrhythmias, and will offer opportunities for restoring or preventing this kind of arrhythmias in the near future. Show less
