Wu Zifei, Huang Xie, Wu Chuan, Zhou Yan, Gao Mingquan, Luo Shenglin, Xiang Qiang, Wang Weidong, Li Rong
Institute of Combined Injury, National Key Laboratory of Trauma and Chemical Poisoning, Army Key Laboratory of Nanomedicine, Department of Military Preventive Medicine, Army Medical University (Third Military Medical University), Chongqing, 400038, China.
Department of Radiation Oncology, Radiation Oncology Key Laboratory of Sichuan Province, Sichuan Clinical Research Center for Cancer, Sichuan Cancer Hospital & Institute, Affiliated Cancer Hospital of University of Electronic Science and Technology of China, Chengdu, 610000, China.
J Nanobiotechnology. 2024 Dec 18;22(1):756. doi: 10.1186/s12951-024-03012-3.
Enhancing the sensitivity of radiotherapy (RT) towards renal cell carcinoma (RCC) remains a challenge because RCC is a radioresistant tumor. In this work, we design and report asymmetrically Polyethylene Glycol (PEG)ylated and amphipathic heptamethine indocyanine dyes for efficient radiosensitization of RCC treatment. They were synthesized by modifying different lengths of PEG chains as hydrophilic moieties on one N-alkyl chain of a mitochondria-targeting heptamethine indocyanine dye (IR-808), and a radiosensitizer 2-nitroimidazole (NM) as a hydrophobic moiety on another N-alkyl chain. The PEG modification significantly improved water solubility, decreased the intermolecular π-π large aggregates, thereby enhanced renal excretion. The asymmetrical and amphipathic modification enhanced the preferential accumulation in renal tumors through self-assembly into small-size nanoparticles in aqueous environment. Radiosensitization was further improved by preferential accumulation in renal tumor cells and their mitochondria as mitochondria play a crucial role in rapid cancer cell growth, metastasis, and RT resistance. Additionally, the modification also increased the abilities of fluorescence emission and photostability, which is meaningful for imaging-guided precise RCC RT. Therefore, our findings may present a theranostic radiosensitizer for renal tumor-targeted imaging and radiosensitization.
提高放射疗法（RT）对肾细胞癌（RCC）的敏感性仍然是一项挑战，因为肾细胞癌是一种放射抗性肿瘤。在这项工作中，我们设计并报道了不对称聚乙二醇（PEG）化的两亲性七甲川吲哚菁染料，用于肾细胞癌治疗的有效放射增敏。它们是通过在靶向线粒体的七甲川吲哚菁染料（IR-808）的一条N-烷基链上修饰不同长度的PEG链作为亲水部分，并在另一条N-烷基链上修饰放射增敏剂2-硝基咪唑（NM）作为疏水部分而合成的。PEG修饰显著提高了水溶性，减少了分子间的π-π大聚集体，从而增强了肾脏排泄。不对称和两亲性修饰通过在水性环境中自组装成小尺寸纳米颗粒，增强了在肾肿瘤中的优先积累。由于线粒体在癌细胞快速生长、转移和放射抗性中起关键作用，通过在肾肿瘤细胞及其线粒体中的优先积累，进一步提高了放射增敏作用。此外，这种修饰还提高了荧光发射能力和光稳定性，这对于成像引导的精确肾细胞癌放射治疗具有重要意义。因此，我们的研究结果可能为肾肿瘤靶向成像和放射增敏提供一种诊疗一体化的放射增敏剂。
