Earth Conversion Nanomaterials For Loading And Delivery Of Hydrophobic Drug Curcumin

In recent years,rare earth upconverting luminescent materials（UCNPs）have unique advantages such as long fluorescence lifetime,small background fluorescence interference,and deep penetration of living tissue,which are a new type of“nano-diagnostic agent”.Therefore,the controlled synthesis,the surface modification and application in the field of bioimaging and drug delivery of rare earth upconversion luminescent materials have attracted more and more attention.In particular,UCNPs are used as energy converters for dynamic therapy（PDT）of tumors under near-infrared light excitation.In this process,upon the suitable excitation light,photosensitizer（PS）molecules can transfer the absorbed photon energy to the surrounding oxygen molecules,and subsequently producing cytotoxic singlet oxygen（¹O₂）or reactive oxygen species（ROS）.At present,there are still the several problems needed to be addressed in the controllable synthesis of UCNPs and their applications in PDT.On the one hand,although rare earth trifluoroacetates and chlorides are commonly used as precursors to synthesize high-quality UNCPs,the two precursors are either expensive or will produce toxic gases in the synthesis process.Herein,it is necessary to develop a simpler and lower-cost method to synthesize UCNPs with monodisperse,uniform morphology and controllable size.On the other hand,currently,most of the photosensitive molecules currently used are ultraviolet/visible light as the excitation light source,but the ultraviolet/visible light has some shortcomings such as low penetration depth and severe damage to normal tissues,which limited their application in biomedical fields.In addition,the vast majority of photosensitizers are hydrophobic and have poor solubility in physiological environments,so they are prone to agglomerate,which reduce their photosensitivity.Therefore,take the above problems in consideration,the research content of this dissertation is as follows:（1）Controlled synthesis of high-quality UCNPs nanocrystals:We successfully synthesized a series of monodisperse,uniform morphology and size controlledβ-NaYF₄:Yb³⁺/Ln³⁺and NaYF₄:Yb³⁺/Ln³⁺@NaGdF₄（Ln=Er,Tm,Ho）core-shell nanoparticles by using a low-cost rare earth hydroxide as the precursor.In addition,we also explored the effects of different reaction conditions on the crystal form,size and morphology of NaYF₄ upconverting nanoparticles such as the molar ratio of Na⁺/Ln³⁺/F^-,sodium source（sodium oleate,sodium fluoride）and the volume ratio of oleic acid（OA）to octadecene（ODE）.In addition,upconversion fluorescence intensity is significantly enhanced by constructing a core-shell structure.（2）UCNPs@SiO₂ yolk-shell nanocomposites as carrier for loading the hydrophobic drug curcumin and PDT treatment:we designed and synthesized UCNPs@SiO₂ with a hollow structure to achieve fine control of pore size,mesoporous shell thickness and overall nanoparticle size by carefully regulating experimental conditions such as the size and concentration of UCNPs,water"etching"temperature and time,etc.As a carrier,it was used to load the hydrophobic drug molecule curcumin which can be excited by blue light.Finally,the application of the material in PDT and the corresponding anti-tumor mechanism were studied systematically.