Construct And Study Of A Novel Hyperpolarized¹²⁹Xe Nanoparticle Probe

Hyperpolarized Xenon has an NMR sensitivity of 10000 times higher than the classical proton NMR.But xenon only has one NMR signal.If hyperpolarized 129Xe could be combined with molecular cages,new 129Xe signals will be obtained,laying a foundation for the development of hyperpolarized 129Xe targeted molecular probes.Therefore,the construction of novel molecular cages is an important direction.At present,the study of the host"molecular cage"is mainly based on cryptophane.However,the cryptic compounds also have the disadvantages of difficulty in synthesis and modification,poor water solubility,etc.Therefore,the development of new molecular cages face great challenge of the hyperpolarized 129Xe magnetic resonance field.Based on the previous studies,this paper synthesizes and screens a series of Xe-capable nanoparLicles with the aim of developing a new hyperpolarized 129Xe molecular probe to determine whether it has the potential to become a hyperpolarized 129Xe molecular probe.The specific content is as follows:1.Seven kinds of nanoparticles based on Cucurbit[6]uril were synthesized and screened for water solubility and 129Xe magnetic resonance signals.Cucurbit[6]uril has been explored as a suitable hyperpolarized 129Xe molecular cage,however,the signal of hyperpolarized 129Xe moleclar probe based on Cucurbit[6]Lril tends to be too broad and weak compared to the molecular cage.It is easy to be masked by noise.At the same time,the poor water solubility and modification difficulty of Cucurbit[6]uril also restrict the development of such molecular probes.In this work,the Cucurbit[6]uril was assembled into nanoparticles in different ways(each nanoparticle contains multiple Cucurbit[6]uril molecular cages,which can achieve signal concentration and enhancement),and then a series of nanoparticles were screened and the water-soluble nanoparticles were selected for further study.In the end,we successfully screened nanoparticles with good water solubility and signal in double "cage"inside the Cucurbit[6]uril/nanoparticle.2.To explore the drug delivery function of the selected Cucurbit[6]uril-based nanoparticles,the 129Xe magnetic resonance test was carried out on the Cucurbit[6]uril-based nanoparticles.It was found that the soluble nanoparticles contained the Xe signal in the double "cage" inside the Cucurbit[6]uril/nanoparticle.Based on the existence of dual signals,we judged that such nanoparticles have the function of accurately delivering hydrophobic drugs.After testing,we verified the accurate drug delivery function of this nanoparticle by fluorescence and 129Xe magnetic resonance method,and the results obtained by the two methods are very consistent.The nanoparticles have good drug loading and release functions,as well as changes in the double CEST signals during drug loading and release,effectively avoiding the occurrence of false positive and false negative signals.3.An auto fluorescent aromatic micelle was synthesized and the basic properties were explored.The molecular micelles have a hydrophobic cavity and a suitable size,which is theoretically possible to be a novel molecular cage.In this work,we synthesized the molecular micelles of this kind polyaromatic shell,and simply tested its particle size and fluorescence properties,and then analyzed xwhether it could become a new 129Xe cage by Hyper-CEST 129Xe magnetic resonance technology.