介孔生物活性玻璃在蛋白降解中的应用
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作者单位:

1.中国科学院深圳先进技术研究院;2.中国科学院大学

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Q599

基金项目:

深圳市医学科研基金(D2301003);深圳市科学技术创新委员会(SGDX20220530111004031,JCYJ20220818100412028)


Application of mesoporous bioactive glass in protein targeted degradation
Author:
Affiliation:

1.Shenzhen Institutes of Advanced Technology, Chinese Academy of Sciences;2.University of Chinese Academy of Sciences

Fund Project:

Shenzhen Medical Research Funds (D2301003); Shenzhen Science and Technology Innovation Commission (Grant Nos. SGDX20220530111004031 andJCYJ20220818100412028);

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    摘要:

    当前,靶向蛋白降解技术面临靶向特异性不足和递送效率低等挑战,而纳米材料的靶向富集特性为克服这些瓶颈提供新思路。介孔生物活性玻璃(MBG)因其高生物相容性和药物递送潜力备受关注,但其作为靶向蛋白降解载体的可行性尚未明确。本研究利用FITC荧光标记和生物素-亲和素体系验证MBG的亚细胞定位及其作为降解载体的可行性。此外,本工作还考察了铁掺杂的MBG诱导铁死亡的潜能。结果显示,MBG能够诱导靶蛋白的内化并进入溶酶体降解,如PD-L1的降解。在此基础上,MBG还能递送铁离子进入溶酶体,诱导铁死亡的发生。该研究首次揭示了MBG兼具靶向蛋白降解与铁死亡诱导的双重功能,为开发“蛋白降解-铁死亡”时空可控协同治疗癌症提供创新性方案。

    Abstract:

    Targeted protein degradation technologies face significant challenges, including insufficient target specificity and low delivery efficiency. Mesoporous bioactive glass (MBG) is a biocompatible nanomaterial widely studied in drug delivery, yet its potential as a platform for targeted protein degradation remains unexplored. In this study, FITC labeling and the biotin-avidin system were employed to evaluate the subcellular localization of MBG and its potential as a protein degradation carrier. Additionally, the ferroptosis-inducing capability of Fe-doped MBG was investigated. The results demonstrated that MBG facilitates the internalization of target proteins and degradation in lysosomes, as exemplified by the degradation of PD-L1. Furthermore, MBG was shown to deliver iron ions into lysosomes, inducing ferroptosis. This study, for the first time, reveals the dual functionality of MBG in targeted protein degradation and ferroptosis induction, offering an innovative approach for the spatiotemporally controlled synergistic treatment of cancer through "protein degradation-ferroptosis" strategies.

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引用本文

余萱,杨长江,崔旭,等.介孔生物活性玻璃在蛋白降解中的应用 [J].集成技术,

Citing format
YU Xuan, YANG Changjiang, CUI Xu, et al. Application of mesoporous bioactive glass in protein targeted degradation[J]. Journal of Integration Technology.

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  • 收稿日期:2025-03-23
  • 最后修改日期:2025-04-11
  • 录用日期:2025-04-21
  • 在线发布日期: 2025-05-07
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