Department of Ultrasound in Medicine, The Second Affiliated Hospital of Zhejiang University School of Medicine, No. 88 Jiefang Road, Shangcheng District, Hangzhou 310009, P. R. China.
Research Center of Ultrasound in Medicine and Biomedical Engineering, The Second Affiliated Hospital of Zhejiang University School of Medicine, Zhejiang University, No. 88 Jiefang Road, Shangcheng District, Hangzhou 310009, P. R. China.
ACS Appl Mater Interfaces. 2022 Sep 14;14(36):40535-40545. doi: 10.1021/acsami.2c08951. Epub 2022 Aug 31.
Sonodynamic therapy (SDT), a noninvasive therapy that relies on sonosensitizers and generates reactive oxygen species (ROS), has attracted considerable attention in the treatment of pancreatic cancer. However, being surrounded by dense stromal barriers, pancreatic cancer exhibits high interstitial fluid pressure (IFP) and hypoxia in the tumor microenvironment (TME), resulting in poor SDT efficacy. Collagenase-loaded hollow TiO (Col-H-TiO) nanoparticles (NPs) capable of degrading stromal barriers and producing sufficient ROS production were synthesized in this study. After administration of NPs in the patient-derived xenograft (PDX) model, ultrasonic irradiation-released collagenase degraded tumor matrix fibers, decreased intratumoral IFP, and enhanced the penetration and retention of NPs within tumor tissues. Moreover, the NPs accumulated within the tumor not only generate abundant ROS under the influence of ultrasound irradiation but also improve intratumoral ultrasound signal, providing ultrasonic imaging-guided highly effective SDT for pancreatic cancer. In conclusion, this research improves the SDT technique and enhances the visualization of pancreatic cancer by remodeling the TME and is a promising strategy for further clinical applications.
声动力学疗法（SDT）是一种非侵入性治疗方法，依赖声敏剂产生活性氧（ROS），在胰腺癌治疗中引起了广泛关注。然而，由于胰腺癌周围存在密集的基质屏障，其肿瘤微环境（TME）中存在高间质流体压力（IFP）和缺氧，导致 SDT 疗效不佳。本研究合成了负载胶原酶的中空 TiO（Col-H-TiO）纳米颗粒（NPs），能够降解基质屏障并产生足够的 ROS 生成。在给予 NPs 后，在患者来源的异种移植（PDX）模型中，超声辐照释放的胶原酶降解肿瘤基质纤维，降低肿瘤内 IFP，并增强 NPs 在肿瘤组织内的穿透和滞留。此外， NPs 在肿瘤内的积累不仅在超声辐照的影响下产生大量 ROS，而且还改善了肿瘤内的超声信号，为胰腺癌提供了超声成像引导的高效 SDT。总之，本研究通过重塑 TME 提高了 SDT 技术并增强了胰腺癌的可视化，是进一步临床应用的有前途的策略。
