Department of Ultrasound, the First Affiliated Hospital of Chongqing Medical University, Chongqing, 400042, P.R. China.
Department of Oncology, the First Affiliated Hospital of Chongqing Medical University, Chongqing, 400042, P.R. China.
J Nanobiotechnology. 2023 Jul 5;21(1):209. doi: 10.1186/s12951-023-01970-8.
Radiotherapy (RT) is one of the most mainstream cancer therapeutic modalities. However, due to the lack of specificity of the radiation adopted, both normal and cancerous cells are destroyed indiscriminately. This highlights the crucial need to improve radiosensitization. This study aims to address this issue by constructing a multifunctional nanospheres that can sensitize multiple aspects of radiotherapy.
Nanospheres containing high atomic element Bi can effectively absorb ionizing radiation and can be used as radiosensitizers. Cell viability after BiS + X-ray treatment was half that of X-ray treatment alone. On the other hand, exposed 3-bromopyruvate (3BP) could reduce the overactive oxygen (O) metabolism of tumor cells and alleviate tumor hypoxia, thereby promoting radiation-induced DNA damage. The combination index (CI) of 3BP and BiS-based RT in BiS-3BP + X-ray was determined to be 0.46 with the fraction affected (f) was 0.5 via Chou-Talalay's isobolographic method, which indicated synergistic effect of 3BP and BiS-based RT after integration into BiS-3BP + X-ray. Under the combined effect of 3BP and RT, autophagy was over-activated through starvation-induced and redox homeostasis dysregulation pathways, which in turn exhibited pro-death effects. In addition, the prepared nanospheres possess strong X-ray attenuation and high near-infrared (NIR) optical absorption, thus eliminating the need for additional functional components and could serve as bimodal contrast agents for computed tomography/photoacoustic (CT/PA) imaging.
The rational design of multifunctional nanospheres with the unique properties provided a novel strategy to achieving high therapeutic efficacy in RT. This was accomplished through simultaneous activation of multiple sensitization pathways by increasing ionizing radiation, reducing tumor oxygen consumption, inducing pro-death autophagy, and providing multiple-imaging guidance/monitoring.
放射治疗（RT）是最主流的癌症治疗方式之一。然而，由于所采用的辐射缺乏特异性，正常细胞和癌细胞都会被无差别破坏。这凸显了提高放射敏化作用的关键需求。本研究旨在通过构建多功能纳米球来解决这个问题，这种纳米球可以从多个方面增强放射治疗效果。
含有高原子元素铋的纳米球可以有效地吸收电离辐射，可用作放射增敏剂。经 BiS+X 射线处理后的细胞活力仅为单独 X 射线处理后的一半。另一方面，暴露于 3-溴丙酮酸（3BP）可降低肿瘤细胞过度活跃的氧（O）代谢，并缓解肿瘤缺氧，从而促进辐射诱导的 DNA 损伤。3BP 和基于 BiS 的 RT 的组合指数（CI）通过 Chou-Talalay 的等和线方法确定为 0.46，分影响（f）为 0.5，表明 BiS-3BP+X 射线中 3BP 和基于 BiS 的 RT 的协同作用。在 3BP 和 RT 的联合作用下，自噬通过饥饿诱导和氧化还原稳态失调途径被过度激活，进而表现出促死亡效应。此外，所制备的纳米球具有很强的 X 射线衰减和高近红外（NIR）光学吸收能力，因此无需额外的功能组件，可作为计算机断层扫描/光声（CT/PA）成像的双模态对比剂。
具有独特性能的多功能纳米球的合理设计为提高放射治疗的疗效提供了一种新策略。这是通过增加电离辐射、减少肿瘤耗氧量、诱导促死亡自噬以及提供多种成像指导/监测来同时激活多种增敏途径来实现的。
