Fang Haoyu, Zhu Daoyu, Chen Yixuan, Zhang Changqing, Li Gan, Fang Qihang, Chang Meiqi, Chen Yu, Gao Youshui
Department of Orthopedic Surgery, Shanghai Sixth People's Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, 200233, China.
Laboratory Center, Shanghai Municipal Hospital of Traditional Chinese Medicine, Shanghai University of Traditional Chinese Medicine, Shanghai, 200071, China.
Adv Sci (Weinh). 2025 Apr 3:e2417208. doi: 10.1002/advs.202417208.
Various antitumor strategies have emerged to address the escalating need for effective tumor eradication. However, achieving precise and spatiotemporally controlled dynamic therapies remains promising yet challenging. Sonopiezoelectric nanotherapy eliminates tumor cells by generating reactive oxygen species (ROS) through ultrasound stimulation, enabling spatiotemporal control and ensuring safety during deep tissue penetration. In this study, a hybrid bioscaffold incorporating few-layer black phosphorus (BP) and nitric oxide (NO) donors are rationally designed and engineered for sonopiezoelectric-gaseous synergistic therapy. This ultrasound-responsive system provides a stepwise countermeasure against tumor invasion in bone tissues. Ultrasonic vibration induces mechanical strain in BP nanosheets, leading to piezoelectric polarization and subsequent ROS generation. Moreover, ultrasound-triggered NO burst release from the donors enables spatiotemporally controlled gas therapy. The synergistic effects of sonopiezoelectric therapy and ultrasound-excited gas therapy enhance tumor eradication, effectively inhibiting tumor proliferation and metastasis while minimizing off-target cytotoxicity. Additionally, the biomineralization capability of degradable BP and proangiogenic effects of low-concentration NO establish the hybrid bioscaffold as a bioactive platform that facilitates subsequent bone regeneration. The development of this 4D multifunctional therapeutic platform, characterized by superior sonopiezoelectric efficacy, controlled NO release, and stimulatory effects on tissue regeneration, offers new insights into the comprehensive treatment of invasive bone tumors.
为满足对有效根除肿瘤日益增长的需求，已出现了各种抗肿瘤策略。然而，实现精确且时空可控的动态治疗仍充满希望但具有挑战性。声压电纳米疗法通过超声刺激产生活性氧（ROS）来消除肿瘤细胞，能够实现时空控制并确保在深部组织穿透过程中的安全性。在本研究中，合理设计并构建了一种包含少层黑磷（BP）和一氧化氮（NO）供体的混合生物支架，用于声压电 - 气体协同治疗。这种超声响应系统为骨组织中的肿瘤侵袭提供了逐步应对措施。超声振动在BP纳米片中诱导机械应变，导致压电极化并随后产生活性氧。此外，超声触发供体释放NO，实现时空可控的气体治疗。声压电疗法和超声激发气体疗法的协同效应增强了肿瘤根除效果，有效抑制肿瘤增殖和转移，同时将脱靶细胞毒性降至最低。此外，可降解BP的生物矿化能力和低浓度NO的促血管生成作用使该混合生物支架成为促进后续骨再生的生物活性平台。这种具有卓越声压电疗效、可控NO释放以及对组织再生具有刺激作用的4D多功能治疗平台的开发，为侵袭性骨肿瘤的综合治疗提供了新的见解。
