摘要
快速消除感染和促进骨再生是骨髓炎临床治疗的两个关键环节.当前迫切需要开发高效的生物活性声敏剂用于声动力治疗(SDT).在此,我们设计了一种二维Nb_(2)C纳米片修饰的卟啉基金属有机框架纳米平台(HNTM/Nb_(2)C)用于在超声辐照下同时消除感染和加速骨再生.通过在HNTM和Nb_(2)C纳米片之间构建肖特基结,实现了超声辐照下快速的电荷转移并抑制电子-空穴对的重组,从而产生丰富的活性氧.这种新型的声敏剂可以加速干细胞向成骨细胞的分化.RNA测序表明,该HNTM/Nb_(2)C纳米平台通过阳离子释放及超声响应电流引起的ATP合成耦合的电子传递诱导干细胞分化.此外,KEGG通路富集分析表明,Nb离子可能通过激活Wnt信号通路进一步促进成骨.我们的研究为骨髓炎的高效SDT提供了新的策略,该策略通过声响应电流联合离子疗法,实现了感染的消除同时促进了骨再生.
Rapid disinfection and promotion of bone regeneration are two crucial aspects of the clinical treatment of osteomyelitis.There is an urgent need to develop highly efficient bioactive sonosensitizers for sonodynamic therapy(SDT).Herein,a type of two-dimensional(2D)Nb_(2)C nanosheet-decorated porphyrin metal-organic framework hollow nanotubes(HNTM/Nb_(2)C)was designed to simultaneously eliminate infection and accelerate bone regeneration under ultrasound(US)irradiation.Building a Schottky junction between HNTM and Nb_(2)C nanosheets allowed enough reactive oxygen species(ROS)to be produced because of the rapid charge transfer and suppressed recombination of electronhole pairs under US irradiation.The sonosensitizer accelerated the osteoblastic differentiation of stem cells.RNAseq indicated that the HNTM/Nb_(2)C nanoplatform induced stem cell differentiation via cation transport and ATPsynthesis-coupled electron transport through an ultrasonic current.Moreover,Kyoto Encyclopedia of Genes and Genomes pathway analysis showed that the Nb ion may further improve osteogenesis via the activation of Wnt signaling.Our study provides novel strategies for improving SDT efficiency by simultaneously eliminating infections and promoting bone regeneration through US-current-combined ion therapy for osteomyelitis treatment.
作者
马良
张晓光
王鸿钏
冯晓波
雷捷
何雅琦
魏君雨
张宇坤
谭磊
杨操
Liang Ma;Xiaoguang Zhang;Hongchuan Wang;Xiaobo Feng;Jie Lei;Yaqi He;Junyu Wei;Yukun Zhang;Lei Tan;Cao Yang(Department of Orthopaedics,Union Hospital,Tongji Medical College,Huazhong University of Science and Technology,Wuhan 430022,China)
基金
supported by the National Natural Science Foundation of China(81902261,22175058,and 81772401)
the Application Foundation and Advanced Program of Wuhan Science and Technology Bureau(2019020701011457)
the Fundamental Research Funds for the Central Universities(2019kfyXMBZ063)。