Abstract:
Preventing local tumor recurrence while promoting bone tissue regeneration is an urgent need for osteosarcoma treatment. However, the therapeutic efficacy of traditional photosensitizers is limited, and they lack the ability to regenerate bone. Here, a piezo-photo nanoheterostructure is developed based on ultrasmall bismuth/strontium titanate nanocubes (denoted as Bi/SrTiO3), which achieve piezoelectric field-driven fast charge separation coupling with surface plasmon resonance to efficiently generate reactive oxygen species. These hybrid nanotherapeutics are integrated into injectable biopolymer hydrogels, which exhibit outstanding anticancer effects under the combined irradiation of NIR and ultrasound. In vivo studies using patient-derived xenograft models and tibial osteosarcoma models demonstrate that the hydrogels achieve tumor suppression with efficacy rates of 98.6 % and 67.6 % in the respective models. Furthermore, the hydrogel had good filling and retention capabilities in the bone defect region, which exerted bone repair therapeutic efficacy by polarizing and conveying electrical stimuli to the cells under mild ultrasound radiation. This study provides a comprehensive and clinically feasible strategy for the overall treatment and tissue regeneration of osteosarcoma.
摘要:
在促进骨组织再生的同时预防局部肿瘤复发是骨肉瘤治疗的迫切需要。然而,传统光敏剂的治疗效果有限,他们缺乏再生骨骼的能力。这里,基于超小的铋/锶钛酸纳米立方体(表示为Bi/SrTiO3)开发了压电-光电纳米异质结构,实现了压电场驱动的快速电荷分离与表面等离子体共振耦合,有效地产生活性氧。这些混合纳米治疗剂被整合到可注射生物聚合物水凝胶中,在近红外和超声联合照射下表现出优异的抗癌作用。使用患者衍生的异种移植模型和胫骨骨肉瘤模型的体内研究表明,水凝胶在各自的模型中以98.6%和67.6%的效率实现了肿瘤抑制。此外,水凝胶在骨缺损区域具有良好的填充和保留能力,在温和的超声辐射下,通过极化和向细胞传递电刺激来发挥骨修复治疗功效。本研究为骨肉瘤的整体治疗和组织再生提供了一个全面的、临床可行的策略。