Construction Of GdF₃:Yb³⁺,Er³⁺ Upconverting Nanoplatform And Its Effect Of Photodynamic Therapy On Liver Cancer Cells

Objective:1.To prepare MPA or PEG modified GdF₃:Yb,Er UCNPs with excellent crystallinity,uniform particle size,high chemical stability,good water solubility,perfect luminescent properties and low cytotoxicity through one-step hydrothermal method.2.In order to obtain the GdF₃:Yb,Er-MPA-HSA-Ce6 nanoplatform with good water solubility and biocompatibility.3.To evaluate the photodynamic effect of GdF₃:Yb,Er-MPA-HSA-Ce6 on liver cancer cells.Methods:1.The synthesis and characterization of PEG or MPA Modified GdF₃:Yb,Er UCNPsOne-pot hydrothermal method was employed to construct PEG-GdF₃:Yb,Er and MPA-GdF₃:Yb,Er UCNPs.Then its phase structure,morphology,luminescent and magnetic properties were analyzed by XRD,TEM,XPS,FTIR,fluorescence spectrophotometer and SQUID-VSM magnetic measurement system,respectively.The cell cytotoxicities of PEG-GdF₃:Yb,Er and MPA-GdF₃:Yb,Er UCNPs were evaluated by MTT.2.The preparation of GdF₃:Yb,Er-MPA-HSA-Ce6 nanoplatform and the evaluation of its PDT effect on liver cancer cellsNanoplatform based on GdF₃:Yb,Er-MPA-HSA-Ce6 was constructed by bio-functionalization method.The loading of Ce6 was qualitatively observed by centrifugation,and the loading rate of Ce6 was further quantitatively determined by UV-Visible spectrophotometer.The changes of morphology,size distribution and dispersion for nanoparticles after bio-functionalization were analyzed by TEM.The effect of bio-functionalization on the luminescent properties of nanoparticles and the FRET between Ce6 and UCNPs were confirmed by fluorescence spectrophotometer.MTT was conducted to evaluate the cytotoxicity of GdF₃:Yb,Er-MPA-HSA-Ce6.The preliminary study about PDT effects of GdF₃:Yb,Er-MPA-HSA-Ce6 on HepG2 cells was carried out.Results:1.The morphology,optical performance and cytotoxicity evaluation of PEG-GdF₃:Yb,Er UCNPs?1?The UCNPs exhibit nearly spherical shape and good dispersiblity.The average nanoparticles size is about 40 nm.Its crystal structure mainly belongs to orthogonal phases GdF₃.?2?The UCL of PEG-GdF₃:Yb,Er under NIR laser excitation has strong blue fluorescence peaks located at 489 nm.At room temperature,it shows remarkable paramagnetism with a magnetic susceptibility of 6.25×10^-55 em?/g·Oe.?3?When the concentration of PEG-GdF₃:Yb,Er is lower than 270?g/mL,the cell viability of both PLC and HepG2 all remains above 90%.When it increases to 810?g/mL,cellular viability of PLC is almost unchanged,but the cell viability of HepG2is obviously reduced.2.The phase structure,optical and magnetic properties and cytotoxicity analysis of MPA-GdF₃:Yb,Er UCNPs?1?The crystal structure of MPA-GdF₃:Yb,Er is mainly consistent with orthorhombic crystal system GdF₃.This nanoparticle shows a uniform nearly spherical structure with a diameter around 40 nm.?2?UCL properties of MPA-GdF₃:Yb,Er is detected under the excitation of a 980 nm laser diode.Blue emission bands centered at 490 nm,the two green emission bands centered at 525 nm and 550 nm and red emission bands centered at 660 nm are observed.And the intensity ratio of fluorescence among the former UCL peaks is close to2:1.5:4:1.It shows obvious paramagnetism at RT,and the susceptibility is about 6.6×10^-55 em?/g·Oe.?3?The cell viability of both PLC and HepG2 cells treated with MPA-GdF₃:Yb,Er UCNPs is all above 90%even at the concentration of 810?g/ml.3.The morphology and luminescent properties of GdF₃:Yb,Er-MPA-HSA-Ce6nanoplatform and its PDT effect on liver cancer cells?1?GdF₃:Yb,Er-MPA-HSA-Ce6 nanoplatform exhibits roughly spherical and monodispersed with an average diameter about 50 nm.The emission feature is similar to that of MPA-GdF3:Yb,Er except that the fluorescence peak at 490 nm is relatively enhanced and the red emission peak centered at 660 nm disappeares.?2?The cell viability for both PLC and HepG2 is all above 85%when the concentration of GdF₃:Yb,Er-MPA-HSA-Ce6 ranges from 0 to 810?g/mL.In in vitro PDT for HepG2 cells,the cell viability at relatively high concentration group??270?g/mL?showes obvious decrease,while the cell viability in the low concentration group??90?g/mL?do not exhibite noticeable decrease.Conclusions:1.PEG-GdF₃:Yb,Er UCNPs are synthesized by one-step hydrothermal method.Its crystal structure is agreed with orthogonal phase GdF₃.It is well dispersed and shows a uniform size distribution.The blue emission peak located at 489 nm of PEG-GdF₃:Yb,Er is the strongest under 980 nm laser illumination.It shows obvious paramagnetism and relatively high susceptibility at room temperature.As-prepared PEG-GdF₃:Yb,Er shows almost no cytotoxicity at low concentration and low cytotoxicity at a relatively high dose.2.MPA-GdF₃:Yb,Er UCNPs prepared in hydrothermal environment exhibit monodisperse with a uniform size.Its crystal structure mainly belongs to GdF₃orthorhombic system.The green emission peaks centered at 550 nm are the strongest when it is excited at 980 nm.The UCNPs also exhibit obvious paramagnetism at RT,and the magnetic susceptibility is relatively high.In addition,it shows no significant cytotoxicity for liver cancer cells.3.The average diameter of GdF₃:Yb,Er-MPA-HSA-Ce6 increases slightly and the dispersion is improved significantly.After bio-functionalization,its luminescence properties have no obvious changes and an effective FRET between Ce6 and UCNPs has been confirmed.No cytotoxic effect of the prepared nanocomposite is found.It showes an outstanding synergistic anti-tumor effect at 270?g/mL,but when the processing concentration gradually reduces,it has no significant PDT treatment effect.