Fundamental Studies on Photothermal Bi-doped Bioglasses

Author:Wang Li Ping

Supervisor:peng ming ying


Degree Year:2019





With the increase of incidence of cancer,the number of cancer deaths is increasing every year worldwide.Cancer treatment is one of the great challenges in the 21st century.Currently,the common treatment methods for bone cancer are surgery,chemotherapy and radiotherapy.However,there are still many problems caused easily by these methods,such as incomplete resection of tumor cells,the defect of normal tissue,strong side effects and so on.Therefore,it is usually necessary to resection multiply tumor cells and repair bone defect.It will provide a new scheme for treating bone tumors by developing a new multi-functional biomaterial that integrates both extinguish residual malignant cells and repair bone tissue.Photothermal(PT)therapy has been considered as one of the treatment methods with minimal damage to human body.However,none of these PT conversion materials involves bioactivity and bone repair.Meanwhile,all the bone repair materials,such as bioglasses or ceramics,have no PT effect simultaneously.In order to achieve multifunctional bioactivity materials with both bone tumor treatment and bone repair,the following research work has been done:First,PT effect of bismuth(Bi)doped glasses was discovered in the germanate system.Under the irradiation of laser power density per unit of 808 nm(1 W/cm2),the temperature of glass sample doped with 2 mol%of Bi2O3 increases by 38.9 oC at a rate of 4.6 oC/s within 90 s.The rate of the increase of temperature is 153 times that of the photothermal Au nanorods.And it is also demonstrated that the PT effect of Bi-doped glass increases linearly with the increase of glass thickness,and it also exhibits superior PT effect under 447 nm,532 nm,808 nm and 980 nm irradiation.Second,four strategies were proposed and demonstrate to enhance PT effect of Bi doped glass based on the mechanism of PT conversion and the principle of energy conservation.The meananism of enhancement is discussed by the evolution of absorption properties,PT effect,NIR luminescence and topological glass network structure.(1)Increasing the amount of absorbed photon.The absorption coefficient of Bi doped germanate glasses G5AxB increases gradually with the increase of Bi 2O3concentration.With the increase of absorbed photon energy,PT effect and Bi NIR luminescence are enhanced simultaneously in the germanate glass samples doped with low concentration Bi2O3(0.001-0.01 mol%),but the extent of the increase of temperature is very little.For the G5AxB samples with high concentration of Bi2O3(0.10-10.0 mol%),Bi NIR luminescence can be gradually weakened.Meanwhile,the PT effect can be enhanced significantly.Subsequently,it is demonstrated that the strategy can also be applied in the Bi doped phosphate glasses,borate glasses and silicate glasses.(2)Decreasing Bi NIR luminescence.Bi NIR luminescence can be enhanced greatly by the addition of Al2O3.With the increase of Al2O3 content,Bi NIR luminescence can be enhanced significantly.Here,Bi NIR luminescence is reduced by decreasing the content of Al2O3 in GxA0.5B glasses,and this thus suppresses the radiation transition.Correspondingly,the energy released by non-radiation transition increases gradually,and thus the PT effect of GxA0.5B glasses is enhanced to some extent.It is proved that the method is also effective in Bi doped silicate and phosphate glasses.(3)Depolymerizing glass network structure.The enhancement of Bi NIR luminescence by the addition of Al2O3 is mainly because the content of glass network formers[AlO4]and[AlO5]is very high in these glass with stronger Bi NIR luminescence.Bi NIR luminescent centers can be dispersed effectively by glass network formed units[AlO4]and network intermediates[AlO5]in these glasses.The interaction among Bi ions can be weakened greatly,and thus reduces the energy loss from non-radiation transition energy.Here,alkali(earth)metal ions as glass network modifiers are introduced to depolymerize the glass network.Correspondingly,Bi NIR luminescence decreases gradually with the addition of alkali(earth)metal,and this thus enhances the non-radiation transition.Correspondingly,the PT effect of Bi doped glasses is enhanced significantly.Combining with the absorption spectra,PT effect and NIR luminescence of Bi doped glasses with different glass substrates,we discovered finally that the strategy can be used merely when the glass samples have the same of absorption coefficient in the alkali(earth)metal ions doped glasses.(4)Instant generation of Bi NIR emission centers in the microprocessing region by femtosecond laser direct writing.Firstly,Bi NIR luminescence center was induced in the microstructure region by femtosecond laser microprocessing.The generation of Bi NIR luminescence center leads to the variation of absorption,PT effect and Bi NIR luminescence in the microstructure region.The content of Bi NIR emission centers increases gradually by increasing the pulse energy of femtosecond laser and modulating the composition of glasses,and thus PT effect of microstructure region inside Bi doped glasses can be enhanced significantly.Third,we selecte appropriate glass compontents with superior PT effect based on the temperature required to kill the tumor and the enhancement strategy of PT,and develop Bi doped silicate bio-glasses with both PT effect and bioactivity.Osteogenic cells can populate,differentiate and mineralize on their surfaces,demonstrating proof of concept to repair bone tissues.They can destroy efficiently bone tumor cells upon808 nm by in vitro and in vivo experiments.After 50 days of co-culture with simulated body fluids,the PT effect decreases slightly.Thus,Bi-doped BGs can assist with toxic chemo-therapies and radiation-therapies,inducing the destruction of residual cancer cells,and they also enable the application of emerging treatment techniques,such as interventional treatment.This thus promotes the development and application of multi-functional biomaterials.