The Construction And Application Of A Nanoplatform Based On TiO₂:Yb,Ho,F

The NIR light-induced theranostic nanosystem has been a promising route to enhance the diagnosis and treatment of tumor,especially for deep tissue.However,the existing UCNP-TiO₂ composites still could not reach ideal photodynamic therapy due to poor energy transfer efficiency.Here,we designed a multifunctional TiO₂:Yb,Ho,F-?-CD@DTX/HA nanoplatform,using Ti O₂:Yb,Ho,F as core,?-CD as shell,hyaluronic acid?HA?as outer shell and target,and then applied for synergetic therapy?photo-chemotherapy?and dual-mode imaging?MRI,UCL?.After doping Yb,Ho,F into TiO₂,it could not only emit green light for imaging in vivo,but also enhanced TiO₂ itself absorption under UV-Vis-NIR region and increased electron-hole pairs separation,thus achieving near-infrared photodynamic therapy.After arriving at tumor,HA shell outside of ?-CD would be degraded by the HAase and release the chemotherapy drug DTX,thus reaching the comnination therapy of photo-chemotherapy.The synthetic processes of TiO₂:Yb,Ho,F-?-CD/DTX@HA nanoparticles were as follows: firstly,the nanoparticle TiO₂:Yb,Ho,F with high upconversion fluorescence effeciency was synthesized by a hydrosol-hydrothermal method.Subsequently,to impart hydrophilicity,TiO₂:Yb,Ho,F was further coated with a thin layer of PEI.Then,TiO₂:Yb,Ho,F-NH2 was coordinated with ?-CD through the an amide bond,allowing for transporting insoluble chemotherapeutic drugs.Finally,HA was attached to the outer surface of TiO₂:Yb,Ho,F-?-CD via electrostatic attraction,which could not only serve as a target but also avoid the drug leaked before reaching the tumor and realized the enzyme-responsive release after being endocytosed by cancer cells.X-ray powder diffraction and X-ray photoelectron spectroscopy confirmed the dopants?Yb,Ho,F?were doped into anatase TiO₂.Transmission Electron Microscopy?TEM?and Transform Infrared Spectroscopy?FT-IR?indicated TiO₂:Yb,Ho,F was successfully coordinated with ?-CD and hyaluronic acid?HA?.Upconversion luminescence spectra?UCL?and the singlet oxygen detection experiments showed the dopants?Yb,Ho,F?improved the upconversion luminescence under 980 nm laser and generated singlet oxygen under 808 nm laser.The drug release assay in vitro suggested TiO₂:Yb,Ho,F-?-CD/DTX@HA exhibited good enzyme-responsive drug release behavior.The vitro antitumor studies : we utilized MCF-7 as cancer cell mode and conducted the cytotoxicity,cellular uptake in vitro,ROS production studies,cell apoptosis and cell cycle arrest.The cytotoxicity and ROS production studies indicated TiO₂:Yb,Ho,F-?-CD/DTX@HA could produce ROS and phototoxicity under 808 nm laser,therefore combining chemotherapeutic drugs?DTX?and inhibiting the growth of MCF-7 cancer cell.The cellular uptake in vitro showed TiO₂:Yb,Ho,F-?-CD /DTX@HA could be uptaken by active targeting ability.The cell cycle arrest and cell apoptosis experiments confirmed TiO₂:Yb,Ho,F-?-CD/DTX@HA could influence the cell cycle and induce cell apoptosis through the comnination therapy of photo-chemotherapy.The vivo antitumor studies:we choosed the KM mouse with S180 tumor as animal model and studied the therapeutic effects in vivo,the pharmacokinetics experiment in vivo,the UCL imaging and MRI imaging in vivo.According to the tumor volume changes,the body weight changes and H&E stained tissues,it proved TiO₂:Yb,Ho,F-?-CD/DTX@ HA could selectively transport DTX to the tumor site through the active targeting effect and kill the tumor through the combination of the photody-namic therapy and chemotherapy under 808 nm.The pharmacokinetic results showed that TiO₂:Yb,Ho,F-?-CD/DTX@HA could significantly prolong the half-life of DTX in vivo.In addition,the up-conversion fluorescence imaging and nuclear magnetic reasonce imaging?MRI?in vivo experiments exhibited that TiO₂:Yb,Ho,F-?-CD/DTX@HA had good up-conversion imaging abilities and magnetic reasonce imaging capabilities in vivo,which could be used to diagnose the tumor and achieve the integration of diagnosis and treatment of cancer.