Study On The Near-infrared-induced Novel Nitrosyl Ruthenium Complex Releasing Nitrous Oxide Form Nanoparticles

Lanthanide-doped Upconversion Nanopaticles（UCNPs）,which have a unique anti-Stokes luminescence-that is,light of a long wavelength can be converted to light of a short wavelength.Due to this unique luminescence property,and its stable chemical properties,low biological toxicity and low fluorescence interference,UCNPs has been widely used in biological detection,drug delivery,biological imaging,photodynamic therapy and other fields.NO-releasing molecules（NORMs）are collectively known as compounds that release NO gas.Most NORMs contain nitroso groups.There are many ways to stimulate NORMs to release NO,including pH excitation,enzymatic excitation and light excitation.Among them,photo-induced nitric oxide releaseing（photo-induced releasing molecules,PhotoNORMs）is a promising approach because of its controllability.Carbohydrates are biological macromolecules involved in life activities,not only providing energy and intracellular tissue support,but also mediating the occurrence of inflammatory reactions,affecting cell growth,division,differentiation,and transduction of intercellular cell signaling.However,low targeted delivery and lack of fluorescent labeling are two major problems with natural polysaccharide drugs.In this paper,UCNPs are used as the host material,and two main tasks have been performed.One is to construct a nano-system capable of releasing NO in the near-infrared-induced;The other work is to use the rhodamine graft GAP to fluorescent labed,using the host-guest interact between rhodamine and cyclodextrin,and build an UCNPs based pH-sensitive drug releases system.The main content can be divided into three parts as follows:（1）Using solvothermal synthesis of sodium tetrafluoro antimony（NaYF₄）,using calcium oleate as the calcium source,doping calcium ions into NaYF₄ crystal lattice,greatly improving crystallinity and size uniformity,and using seed crystal method coating NaGdF₄shell,the result product has an luminescence intensity 100 times higher than that of the No Ca doped.In the UV and visible region,the intensity is increased by 302 times,laying the foundation for further application.（2）According to the reported literature,（1）Ru（NO）Cl compound was synthesized,which can release NO under low energy UV excitation.The Ru（NO）Cl₃ intermediate compounds were synthesized by a simple and efficient method.Through the modification of calcium-doped core-shell UCNPs with methyl-β-CD,the UCNPs are converted from hydrophobic to hydrophilic,and has the ability to be loaded with drugs,and then（1）Ru（NO）Cl is loaded into UCNPs.Under the excitation of near-infrared light at 980 nm,the complex releases NO.The biological toxicity of the complex on SWWC1116 cells was evaluated by MTT assay.It was found that the compound had no obvious biological toxicity to cells in dark conditions,but had certain toxicity to cells after light irradiation.（3）A pH-sensitive drug delivery system was constructed by using the host-guest interaction between rhodamine（R）and cyclodextrin.The R-GAP is formed by grafting rhodamine onto GAP.Then,theβ-NaYF₄:Yb³⁺/Er³⁺nanoparticles was synthesized and modified byβ-CD to make them hydrophilic.By using Rhodamines that changing the conformation with pH,the R-GAP was loaded on the UCNPs under alkaline conditions.R-GAP released in an acidic environment,using the FRET effect between UCNPs and rhodamine to detect the release process.The UV-visible absorption spectrum was used to measure the content of R-GAP released at different pH values.The maximum release amount was 67%at pH=5.5.MTT method was used to evaluate the inhibitory effect of the system on SWWC116 cells,and had a good effect.Confocal laser scanning showed that R-GAP released into the cytoplasm.