Selective and spatiotemporal‑resolved nano-PROTAC for lung cancer therapy

IF 5.6 2区医学 Q1 BIOPHYSICS

Colloids and Surfaces B: Biointerfaces Pub Date : 2025-09-08 DOI:10.1016/j.colsurfb.2025.115135

Xiaowei Xu , Le Wang , Shitao Lin , Xiaoqing Wu , Xufeng Lin , Xiaoling Guan , Shiqi Tang , Ni Zhang , Yuxin Zhang , Lingmin Zhang , Dazhi Zhou

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引用次数: 0

Abstract

The Proteolysis-Targeting Chimeras (PROTAC) technology has become a promising tool in lung cancer therapy. The PROTAC regents targeting to Bromodomain-containing Protein 4 (BRD4) showed effective induction of apoptosis in lung cancer cells. However, the application of this kind of PROTAC regents is still hindered by the low tissue specificity, solubility, and detectability. Herein, we developed a selective and spatiotemporal‑resolved nano-PROTAC, which was constructed using the functional polymer Poly(lactic-co-glycolic acid)-Polyethylene glycol 2000-Maleimide (PLGA-PEG-Mal) to load PROTAC regent dBET6 and the fluorescence dye, and further modification with aptamer targeting to the lung cancer cells. The drug-loaded nanoparticles can be uptaken by lung cancer cells effectively, inducing the complete degradation of BRD4 and effective apoptosis of lung cancer cells. In vivo experiments indicated that the aptamer-modified nanoparticles accumulated in the tumors, which led to the effective suppression of tumor growth in the tumor-bearing mouse model. Furthermore, this type of nano-PROTAC was endowed with real-time tracking capability, avoiding the extra and tedious modifications. The integrated diagnosis and treatment system showed great promise in lung cancer therapy.

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选择性和时空分辨纳米protac用于肺癌治疗

靶向蛋白水解嵌合体（Proteolysis-Targeting Chimeras， PROTAC）技术已成为肺癌治疗中一个很有前途的工具。靶向含溴域蛋白4 （Bromodomain-containing Protein 4, BRD4）的PROTAC试剂可有效诱导肺癌细胞凋亡。然而，这种PROTAC试剂的应用仍然受到组织特异性、溶解度和可检测性较低的阻碍。本研究以聚乳酸-羟基乙酸-聚乙二醇2000-马来酰亚胺（PLGA-PEG-Mal）为功能聚合物，负载PROTAC试剂dBET6和荧光染料，利用适体靶向肺癌细胞，构建了具有选择性和时空分辨率的纳米PROTAC。载药纳米颗粒可被肺癌细胞有效吸收，诱导BRD4完全降解，有效凋亡肺癌细胞。体内实验表明，适体修饰的纳米颗粒在肿瘤中积累，从而有效抑制荷瘤小鼠模型中的肿瘤生长。此外，这种类型的纳米protac具有实时跟踪能力，避免了额外和繁琐的修改。综合诊疗系统在肺癌治疗中具有广阔的应用前景。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Colloids and Surfaces B: Biointerfaces 生物-材料科学：生物材料

CiteScore

11.10

自引率

3.40%

发文量

730

审稿时长

42 days

期刊介绍： Colloids and Surfaces B: Biointerfaces is an international journal devoted to fundamental and applied research on colloid and interfacial phenomena in relation to systems of biological origin, having particular relevance to the medical, pharmaceutical, biotechnological, food and cosmetic fields. Submissions that: (1) deal solely with biological phenomena and do not describe the physico-chemical or colloid-chemical background and/or mechanism of the phenomena, and (2) deal solely with colloid/interfacial phenomena and do not have appropriate biological content or relevance, are outside the scope of the journal and will not be considered for publication. The journal publishes regular research papers, reviews, short communications and invited perspective articles, called BioInterface Perspectives. The BioInterface Perspective provide researchers the opportunity to review their own work, as well as provide insight into the work of others that inspired and influenced the author. Regular articles should have a maximum total length of 6,000 words. In addition, a (combined) maximum of 8 normal-sized figures and/or tables is allowed (so for instance 3 tables and 5 figures). For multiple-panel figures each set of two panels equates to one figure. Short communications should not exceed half of the above. It is required to give on the article cover page a short statistical summary of the article listing the total number of words and tables/figures.