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X-rays-optimized delivery of radiolabeled albumin for cancer theranostics.
Biomaterials ( IF 10.317 ) Pub Date : 2020-01-07 , DOI: 10.1016/j.biomaterials.2020.119764
Xuan Yi,Hailin Zhou,Zheng Zhang,Saisai Xiong,Kai Yang

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.
更新日期:2020-01-07

 

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