Wang Peng,Zhou Xiaosong,Lv Caili,Wang Yu,Wang Zongliang,Wang Liqiang,Zhu Yongzhan,Guo Min,Zhang Peibiao
The endogenous electrical potential generated by native bone and periosteum plays a key role in maintaining bone mass and quality. Inspired by the electrical properties of bone, different negative surface potentials are built on microspheres to restore electric microenvironment for powerful bone regeneration, which was prepared by the combination of strontium-doped barium titanate (Sr-BTO) nanoparticles and poly (lactic-co-glycolic acid) (PLGA) with high electrostatic voltage field (HEV). The surface potential was modulated through regulating the phase composition of nanoparticles in microspheres by the doping amount of strontium ion (Sr2+). As a result, the 0.1Sr-BTO/PLGA group shows the lowest surface potential and its relative permittivity is closer to natural bone. As expected, the 0.1Sr-BTO/PLGA microspheres performed cytocompatibility, osteogenic activity in vitro and enhance bone regeneration in vivo. Furthermore, the potential mechanism of Sr-BTO/PLGA microspheres to promote osteogenic differentiation was further explored. The lower surface potential generated on Sr-BTO/PLGA microspheres regulates cell membrane potential and leads to an increase in the intracellular calcium ion (Ca2+) concentration, which could activate the Calcineurin (CaN)/Nuclear factor of activated T-cells (NFAT) signaling pathway to promote osteogenic differentiation. This study established an effective method to modulate the surface potential, which provides a prospective exploration for electrical stimulation therapy. The 0.1Sr-BTO/PLGA microsphere with lower surface potential and bone-matched dielectric constant is expected to have great potential in the field of bone regeneration.
Yunchao Zhao,Shaobo Wang,Shuncheng Yao,Xingyi Wan,Quanhong Hu,Minjia Zheng,Zhuo Wang,Linlin Li
The efficacy of sonodynamic therapy (SDT) mainly relies on the sonosensitizers, which generate reactive oxygen species (ROS) upon ultrasound (US) stimulation. However, the limited availability of high-efficiency sonosensitizers hampers the therapeutic effectiveness of SDT as a standalone modality. In this work, a robust sonodynamic and gas cancer therapeutic platform is constructed based on strontium (Sr) doped barium titanate (BST) piezoelectric nanoparticles functionalized with L-arginine (BST@LA). The doping of Sr into A site of the ABO 3 piezoelectric nanocrystals not only introduces oxygen vacancies into the nanoparticles and enhance the intrinsic piezoelectricity, but also narrows the semiconductor band gap and enhances charge carrier migration, all of which facilitate the sonodynamic production of superoxide anion (•O 2 − ) and hydroxyl radical (•OH). In addition, the generated ROS promotes the decomposition of the surface-tethered LA, enabling the controlled release of nitric oxide (NO) gas at the tumor site, thereby achieving a combination therapeutic effect. In vivo experiments exhibit remarkable tumor suppression rate (89.5%) in 4T1 tumor mice model, demonstrating the effectiveness of this strategy. The ion doping and oxygen vacancy engineering to improve sonosensitizers, along with the synergistic combination of sonodynamic and gas therapy, provides promising avenues for improving cancer therapy.
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