摘要
For the therapy and regeneration of bone defects resulting from malignant bone tumors, it is necessary to develop multifunctional biomaterials that are able to deliver therapeutic drugs, monitor drug release, and stimulate bone formation. Herein, a multifunctional mesoporous bioactive glass （MBG）/upconversion nanoparticle （UCNP） nanocomposite [UCNPs@SiO2@mSiO2-XCa （X = 0, 5, 10, 15, and 20）] with the ability to deliver anti-cancer drugs, monitor drug release, and stimulate osteogenic differentiation of bone marrow stromal cells （BMSCs） was successfully prepared using a layer-by-layer strategy. The nanocomposite spheres possess a core--sheU structure composed of UCNPs and a mesoporous SiO2/Ca layer with a uniform size distribution of 100 nm. The incorporation of Ca into the nanocomposites induced phase transformation from a pure hexagonal phase to a cubic phase, and facilitated the occurrence of red emission, which significantly improved fluorescence penetration for deep tissue imaging. In addition, since the red emission strongly overlaps with the maximum absorbance of the anti-cancer drug zinc phthalocyanine （ZnPc）, red luminescence could be strongly quenched by ZnPc. Consequently, drug release could be quantified by monitoring changes in fluorescence intensity. Furthermore, the incorporation of Ca into MBG/UCNP nanocomposites remarkably improved bioactivity, i.e., it stimulated apatite mineralization in simulated body fluids and enhanced cell proliferation and bone-related gene expression in BMSCs for the concentration range of 200-500 ~g/mL. Our results suggest that the prepared MBG/UCNP nanocomposites are useful for the therapy and regeneration of bone defects resulting from malignant bone tumors owing to their distinct multifunctionality, including strong red emission and functions in drug-delivery monitoring and osteostimulation.
For the therapy and regeneration of bone defects resulting from malignant bone tumors, it is necessary to develop multifunctional biomaterials that are able to deliver therapeutic drugs, monitor drug release, and stimulate bone formation. Herein, a multifunctional mesoporous bioactive glass （MBG）/upconversion nanoparticle （UCNP） nanocomposite [UCNPs@SiO2@mSiO2-XCa （X = 0, 5, 10, 15, and 20）] with the ability to deliver anti-cancer drugs, monitor drug release, and stimulate osteogenic differentiation of bone marrow stromal cells （BMSCs） was successfully prepared using a layer-by-layer strategy. The nanocomposite spheres possess a core--sheU structure composed of UCNPs and a mesoporous SiO2/Ca layer with a uniform size distribution of 100 nm. The incorporation of Ca into the nanocomposites induced phase transformation from a pure hexagonal phase to a cubic phase, and facilitated the occurrence of red emission, which significantly improved fluorescence penetration for deep tissue imaging. In addition, since the red emission strongly overlaps with the maximum absorbance of the anti-cancer drug zinc phthalocyanine （ZnPc）, red luminescence could be strongly quenched by ZnPc. Consequently, drug release could be quantified by monitoring changes in fluorescence intensity. Furthermore, the incorporation of Ca into MBG/UCNP nanocomposites remarkably improved bioactivity, i.e., it stimulated apatite mineralization in simulated body fluids and enhanced cell proliferation and bone-related gene expression in BMSCs for the concentration range of 200-500 ~g/mL. Our results suggest that the prepared MBG/UCNP nanocomposites are useful for the therapy and regeneration of bone defects resulting from malignant bone tumors owing to their distinct multifunctionality, including strong red emission and functions in drug-delivery monitoring and osteostimulation.
基金
Funding for this study was provided by the China Postdoctroal Science Foundation funded project （No. 2014M561526）, the Recruitment Program of Global Young Talent, China （Dr. Wu）, the National High-tech R＆D Program of China （No. SS2015AA020302）, the National Natural Science Foundation of China （No. 81190132）, Program of Shanghai Outstanding Academic Leaders （No. 15XD1503900）, and the Key Research Program of Chinese Academy of Sciences （No. KGZD- EW-T06）.
