Morphology-directed radiosensitization of MoSe2 nanoplatforms for promoting cervical cancer radiotherapy
Morphology-directed radiosensitization of MoSe2 nanoplatforms for promoting cervical cancer radiotherapy
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DOI：
10.1016/j.nantod.2022.101598
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发表时间：
2022-09-06
期刊：
影响因子：
17.4
通讯作者：
Zhu, Xueqiong
中科院分区：
文献类型：
--
作者：
Jiang, Wenxiao;Zhang, Zhongyang;Zhu, Xueqiong
放射抵抗已成为宫颈癌放射治疗的主要障碍。因此，迫切需要开发有效的放射增敏剂来提高放射治疗效果。MoSe 2由于其窄的禁带宽度和良好的光电/光热转换能力而被认为是一种很有前途的治疗性纳米平台，可用于放射/光介导的癌症治疗，而这些物理性质和生物学性能取决于其结构。本文以2D纳米片（NS）和3D纳米花（NF）两种常见形态的MoSe 2纳米材料为基础，构建放射增敏纳米系统，并对比分析其治疗宫颈癌的疗效和机制。在Hela和Siha细胞上的体外实验证明MoSe 2 NF-RGD优于MoSe 2 NS-RGD的上级协同治疗功效。进一步的分析显示，与MoSe 2 NS-RGD相比，MoSe 2 NF-RGD有效地靶向并积累在癌细胞线粒体中，导致与p53磷酸化相关的线粒体介导的细胞凋亡。此外，MoSe 2 NF-RGD的代谢产物硒代半胱氨酸（SeCys（2））和甲基硒代半胱氨酸（MeSeCys 2）也是其独特的放射增敏抗癌作用的原因。体内实验证实，MoSe 2 NF-RGD联合X射线可通过促进树突状细胞（DCs）和NK 1.1细胞等特异性免疫细胞的浸润，对原发瘤和远处转移瘤均有较好的治疗效果。总的来说，这项工作揭示了材料结构对MoSe 2基纳米系统生物性能和放射治疗功效的影响，以及这些结构依赖性差异的潜在机制。(c)2022爱思唯尔有限公司版权所有。
Radioresistance has been the main obstacle of cervical cancer radiotherapy. Hence, it's urgent need to develop effective radiosensitizers for improving the radiotherapeutic efficacy. MoSe2 has been recognized as a promising therapeutic nanoplatform in radio/photo-mediated cancer therapy, due to its narrow bandgap and good photoelectric/photothermal conversion capabilities, while these physical properties and its bio-logical performance can be various depending on its structure. Herein, radiosensitization nanosystems based on two common forms of MoSe2 nanomaterial, 2D nanosheet (NS) and 3D nanoflower (NF), were developed, and their therapeutic efficacy and mechanisms in treating cervical cancer were contrastively analyzed. In vitro experiments on Hela and Siha cells demonstrated superior synergistic therapeutic efficacy of MoSe2 NF-RGD over MoSe2 NS-RGD. Further analysis revealed that compared to MoSe2 NS-RGD, MoSe2 NF-RGD efficiently targeted and accumulated in cancer cell mitochondria, leading to mitochondria -medi-ated apoptosis associated with p53 phosphorylation. Moreover, the metabolites of MoSe2 NF-RGD including selenocystine (SeCys(2)) and methylselenocysteine (MeSeCys2) also contributed to its unique advantages in radiosensitized cancer-killing effect. Consistently, in vivo study confirmed higher therapeutic efficacies of MoSe2 NF-RGD combined with X-ray against the primary tumor as well as distant tumor through boosting the infiltration of some specific immune cells including dendritic cells (DCs) and NK1.1 cells. Collectively, this work revealed the influence of material structure on the biological performance and radiotherapeutic efficacy of MoSe2-based nanosystems and the underlying mechanisms for these structure-dependent difference.(c) 2022 Elsevier Ltd. All rights reserved.