Design,Synthesis And Applications Of Amorphous Calcium Carbonate-based Nano-Biomaterials

Calcium-based biomaterials have been widely utilized in many biomedical field including bioimaging and biotherapies owing to their excellent biocompatibility,biodegradability and bioactivity.Calcium carbonate,as one of the most common calcium-based biomaterials,has attracted extensive attention for developing pH-responsive nanocarriers and ultrasound imaging contrasts,because of its intrinsic gas-generating properties in the acid environment as well as the excellent biocompatibility,bioactivity and biodegradability.Compared with the traditional micron-scale crystallized CaCO3,amorphous calcium carbonate(ACC)nanomaterials have more potential for biomaterials applications since they are smaller in size and more flexible to be further engineered.However,the poor dispersibility and uniformity of ACC produced by traditional methods as well as the intrinsic unstable property have largely limited their bioapplications.The crucial problem to further develop ACC-based biomaterials is how to overcome and take advantage of their instability.This dissertation will mainly introduce the design.synthesis and bioapplications of ACC-based biomaterials.ACC nanoparticles with excellent monodispersity and uniformity have been produced and silica coated to control its stability.Various functional composites were then constructed by different treatments and modifications.Finally,bioapplications including drug delivery,controlled release,chemotherapy,photothermal therapy and photodynamic therapy effects were realized.The main contents and results can be concluded as follows:1.A series of inorganic nanocarriers were constructed by a facile "one-step acid treatment" method,which were denoted as doxorubicin-calcium@silica nanoparticles(DOX-Ca@silica NPs).The tunable degradability and controlled drug release property of the DOX-Ca@silica NPs were investigated on the basis of the degradable silica framework in the physiological environment.After the acid treatment,the nanocarriers with different amount and distribution of the inner calcium were produced according to the concentration of the acid.Then the differences of the silica shell degradability as well as the drug release behavior caused by the calcium salt-assisted silica decomposition were studied in the physiological environment.At last,the cell-killing effects both in HeLa cells and in drug-resistant MCF-7 tumor cells were investigated in vitro.2.We designed and synthesized amorphous calcium carbonate-doxorubicinC@silica-indocyanine green(A-D@S-I)nanospheres with high monodispersity and uniformity.These nanospheres were used for co-delivery of ICG and DOX molecules in order to combine photothermal and photodynamic agents with chemotherapeutic drugs.The morphology,structure,controlled drug release behavior,photothermal effects and photodynamic effects were characterized and determined.The combined effects of photothermal therapy,photodynamic therapy and chemotherapy were finally studied in DOX-resistant human breast cancer cells to verify the synergistic effects of ICG and DOX molecules.3.Hollow silica and titania nanospheres were synthesized by using ACC NPs as hard templates.The ACC NPs with high monodispersity and uniformity were simply produced,which guaranteed the quality of the template and decreased the cost.Gentle treatment instead of harsh methods like high temperature calcination,strong acid or base was adapted to remove the ACC template.Various conditions during the synthesis were optimized.The hollow silica nanoparticles were used to encapsulate different kinds of dyes and drugs.