X-rays-optimized delivery of radiolabeled albumin for cancer theranostics
X-rays-optimized delivery of radiolabeled albumin for cancer theranostics
复制标题
用于癌症治疗诊断的放射性标记白蛋白的 X 射线优化输送
DOI：
10.1016/j.biomaterials.2020.119764
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发表时间：
2020
期刊：
影响因子：
14
通讯作者：
Yang Kai
中科院分区：
文献类型：
--
作者：
Yi Xuan;Zhou Hailin;Zhang Zheng;Xiong Saisai;Yang Kai
利用X射线照射辅助的可代谢纳米药物的特定生物学行为，将有利于优化放射治疗的综合治疗。本文以人血清白蛋白(HSA)这一常见的可代谢纳米材料为研究对象，研究了X射线照射下肿瘤蓄积和滞留的变化。Caveolin-1是一种重要的蛋白质，与细胞对纳米材料的摄取呈正相关，在X射线照射下表达增加，导致HSA纳米粒子对细胞的摄取增强，肿瘤滞留时间延长。HSA经放射性碘-125标记后，可用于小鼠SPECT/CT显像。此外，研究还发现，125I-HSA纳米粒在照射前肿瘤中的滞留时间比对照肿瘤长得多。采用这一策略，注射~(131)I-HSA的小鼠在X射线照射肿瘤后的治疗效果好于相反顺序处理的小鼠。为了进一步提高人血清白蛋白的靶向能力，将GNQEQVSPLTLLKXC肽(A15)偶联到人血清白蛋白纳米粒上，靶向X射线照射引发的肿瘤组织中的血栓形成，实现了~(131)I-HSA在X射线照射辅助下的高肿瘤蓄积。因此，利用X光照射下Caveolin-1表达增加和诱导血栓形成的优势，我们通过提高细胞摄取和延长肿瘤滞留时间来优化放射性标记HSA的输送，用于癌症联合治疗。为指导临床白蛋白为主的联合治疗做出了贡献。
Exploiting the specific biological behaviors of the metabolizable nano-drugs assisted by X-rays exposure will be.benefit for the optimization of radiotherapy-based combination therapy. Herein, Human serum albumin (HSA).nanoparticle, a familiar and metabolizable nanomaterial, is selected to investigate the changes of tumor accumulation and retention under X-rays exposure. Caveolin-1, an important protein which has positive correlation.with cell uptake of nanomaterials, is expressed increasingly under X-rays exposure, resulting the enhanced cell.uptake and prolonged tumor retention of HSA nanoparticles. After being labeled by radioactive iodine-125, HSA.could be used for SPECT/CT imaging of mice. Moreover, it discovered that 125I-HSA nanoparticles possess much.longer-time retention time in pre-irradiated tumor than that of controlled tumor. Using this strategy, the therapeutic efficiency of 131I-HSA injected mice after irradiating their tumors by X-rays is better than that of opposite.sequence treated mice. In order to further improve the targeting ability of HSA, GNQEQVSPLTLLKXC peptide.(A15) is conjugated to HSA nanoparticles for targeting the thrombosis in the tumor tissue triggered by X-rays.exposure, realizing the high tumor accumulation of 131I-HSA assisted by X-rays exposure. Therefore, taking.advantage of the increased expression of Caveolin-1 and the induced thrombosis under X-rays exposure, we.optimized the delivery of radiolabeled HSA via enhancing the cell uptake and prolonging tumor retention of HSA.for cancer combination therapy. Our work make contribution to guide the clinical albumin based combination.therapy.