接近红外可激活的PROTAC纳米用于可控制的向蛋白质降解和按需的抗瘤治疗
Qi He1, Liming Zhou2, Daxin Yu1
1State Key Laboratory of Natural Medicines, China Pharmaceutical University, 24 Tong Jia Xiang, Nanjing 210009, People's Republic of China.
Journal of medicinal chemistry
|June 6, 2023
概括
研究人员开发了一种通过纳米粒子 (UMSNs@phoBET1) 传递的新型光PROTAC (phoBET1). 该系统可使用近红外光对含有原蛋白的蛋白4 (BRD4) 进行可控的降解,从而提高了癌症治疗的精度.
科学领域:
- 生物化学 生物化学
- 纳米技术纳米技术
- 在瘤学瘤学.
背景情况:
- 针对蛋白质溶解的嵌合体 (PROTACs) 提供有针对性的蛋白质降解,但面临着非目标毒性的挑战.
- 由于潜在的全身毒性,不受控制的PROTAC活性限制了它们的治疗应用.
研究的目的:
- 通过近红外 (NIR) 光激活来设计可控制的 PROTAC 系统.
- 开发一个纳米平台,用于有针对性的交付和光触发释放光PROTACs.
- 研究NIR可激活PROTACs在癌症治疗中的有效性.
主要方法:
- 一个照相PROTAC (phoBET1) 的设计,并将其封装在基于UCNP的半孔纳米粒子 (UMSNs) 中.
- 构建一个可通过NIR光激活的PROTAC纳米 (UMSNs@phoBET1).
- 评估BRD4降解,癌细胞亡诱导和体内瘤抑制在NIR光照射后.
主要成果:
- 在980nm NIR光照射下,UMSNs@phoBET1纳米成功释放了活性PROTAC.
- 在MV-4-11癌细胞中,NIR光激活的PROTACs有效降解含原蛋白蛋白4 (BRD4),诱导亡.
- 在体内研究表明瘤特异性的BRD4降解和显著的瘤生长抑制响应NIR光.
结论:
- 开发的NIR光可激活的PROTAC纳米平台提供了对蛋白质降解的精确控制.
- 该系统克服了短波长光控制的PROTACs的局限性,提供了更安全,更有效的癌症治疗策略.
- 这种纳米平台在活体组织中对PROTACs的精确调节方面取得了重大进展.
更多相关视频
05:33High-Throughput Cellular Profiling of Targeted Protein Degradation Compounds Using HiBiT CRISPR Cell Lines
Published on: November 9, 2020
9.8K
10:10Spatiotemporally Controlled Nuclear Translocation of Guests in Living Cells Using Caged Molecular Glues as Photoactivatable Tags
Published on: January 17, 2019
10.5K
相关概念视频
02:57Targeted Cancer Therapies
7.7K
The targeted cancer therapies, also known as “molecular targeted therapies,” take advantage of the molecular and genetic differences between the cancer cells and the normal cells. It needs a thorough understanding of the cancer cells to develop drugs that can target specific molecular aspects that drive the growth, progression, and spread of cancer cells without affecting the growth and survival of other normal cells in the body.
There are several types of targeted therapies against...
There are several types of targeted therapies against...
7.7K
02:26Protein Networks
4.0K
An organism can have thousands of different proteins, and these proteins must cooperate to ensure the health of an organism. Proteins bind to other proteins and form complexes to carry out their functions. Many proteins interact with multiple other proteins creating a complex network of protein interactions.
These interactions can be represented through maps depicting protein-protein interaction networks, represented as nodes and edges. Nodes are circles that are representative of a protein,...
These interactions can be represented through maps depicting protein-protein interaction networks, represented as nodes and edges. Nodes are circles that are representative of a protein,...
4.0K