State Key Laboratory of Supramolecular Structure and Material, College of Chemistry, Jilin University, Changchun, 130012, China; Shandong Laboratory of Advanced Materials and Green Manufacturing at Yantai, Yantai, 264006, China.
Department of Radiation Oncology, The Second Affiliated Hospital of Jilin University, Changchun, 130041, China.
Biomaterials. 2025 Feb;313:122814. doi: 10.1016/j.biomaterials.2024.122814. Epub 2024 Sep 4.
Radiotherapy as a mainstay of in-depth cervical cancer (CC) treatment suffers from its radioresistance. Radiodynamic therapy (RDT) effectively reverses radio-resistance by generating reactive oxygen species (ROS) with deep tissue penetration. However, the photosensitizers stimulated by X-ray have high toxicity and energy attenuation. Therefore, X-ray responsive diselenide-bridged mesoporous silica nanoparticles (DMSNs) are designed, loading X-ray-activated photosensitizer acridine orange (AO) for spot blasting RDT like Trojan-horse against radio-resistance cervical cancer (R-CC). DMSNs can encapsulate a large amount of AO, in the tumor microenvironment (TME), which has a high concentration of hydrogen peroxide, X-ray radiation triggers the cleavage of diselenide bonds, leading to the degradation of DMSNs and the consequent release of AO directly at the tumor site. On the one hand, it solves the problems of rapid drug clearance, adverse distribution, and side effects caused by simple AO treatment. On the other hand, it fully utilizes the advantages of highly penetrating X-ray responsive RDT to enhance radiotherapy sensitivity. This approach results in ROS-induced mitochondria damage, inhibition of DNA damage repair, cell cycle arrest and promotion of cancer cell apoptosis in R-CC. The X-ray responsive DMSNs@AO hold considerable potential in overcoming obstacles for advanced RDT in the treatment of R-CC.
放射疗法作为深入治疗宫颈癌（CC）的主要手段，但其存在放射抵抗性。放射动力疗法（RDT）通过产生具有深层组织穿透能力的活性氧物种（ROS），有效地逆转了放射抵抗性。然而，X 射线刺激的光敏剂具有高毒性和能量衰减。因此，设计了 X 射线响应的二硒键桥接介孔硅纳米粒子（DMSNs），负载 X 射线激活的光敏剂吖啶橙（AO），用于定点爆破像特洛伊木马一样针对放射抵抗性宫颈癌（R-CC）的 RDT。DMSNs 可以封装大量的 AO，在肿瘤微环境（TME）中，过氧化氢浓度很高，X 射线辐射会触发二硒键的断裂，导致 DMSNs 的降解，并直接在肿瘤部位释放 AO。一方面，它解决了单纯 AO 治疗引起的药物快速清除、不良分布和副作用的问题。另一方面，它充分利用了高穿透性 X 射线响应 RDT 的优势，增强了放射治疗的敏感性。这种方法导致 ROS 诱导的线粒体损伤、抑制 DNA 损伤修复、细胞周期停滞和促进 R-CC 中的癌细胞凋亡。X 射线响应的 DMSNs@AO 在克服高级 RDT 在治疗 R-CC 中的障碍方面具有相当大的潜力。
