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已发表论文
纳米技术推动蛋白水解靶向嵌合体（PROTACs）的发展：从基础研究到临床应用的转变
Authors Mu X , Mu C, Wang M, Meng C, Liu H, Lu H
Received 9 July 2025
Accepted for publication 30 September 2025
Published 6 October 2025 Volume 2025:20 Pages 12177—12198
DOI https://doi.org/10.2147/IJN.S552644
Checked for plagiarism Yes
Review by Single anonymous peer review
Peer reviewer comments 2
Editor who approved publication: Professor Eng San Thian
Xupeng Mu,1,* Chongqiang Mu,2,* Mengxue Wang,2 Chen Meng,2 Huimin Liu,2 Haibin Lu2
1Scientific Research Center, China-Japan Union Hospital of Jilin University, Changchun, Jilin Province, 130033, People’s Republic of China; 2Jilin University School of Pharmaceutical Sciences, Changchun, Jilin Province, 130021, People’s Republic of China
*These authors contributed equally to this work
Correspondence: Haibin Lu, Email luhaibin@jlu.edu.cn
Abstract: Proteolysis Targeting Chimeras (PROTACs) have been extensively explored for the targeted degradation of disease-associated proteins due to their therapeutic ability to modulate proteins that are difficult to target by conventional small molecules, showing vast potential in treating refractory diseases such as cancer and neurodegenerative disorders. However, the clinical application of PROTACs is limited by their large molecular weight, low solubility, poor permeability, and the “hook effect”. Fortunately, the rapid advancement of nanotechnology offers new strategies to overcome some of the key challenges faced by traditional PROTAC technologies, potentially facilitating their clinical translation. In this review, we outline the mechanisms of action of PROTACs and explore their potential clinical significance, along with the main challenges in delivering these compounds. Additionally, we comprehensively summarize recent advancements in nanotechnology for enhancing the delivery efficiency of PROTAC drugs and discuss the limitations of current strategies and future perspectives. In conclusion, this review aims to deepen researchers’ understanding of this strategy, thereby advancing the clinical translation of PROTAC drugs and providing more effective strategies for treating complex, refractory diseases.
Keywords: PROTACs, nanotechnology, clinical application
1Scientific Research Center, China-Japan Union Hospital of Jilin University, Changchun, Jilin Province, 130033, People’s Republic of China; 2Jilin University School of Pharmaceutical Sciences, Changchun, Jilin Province, 130021, People’s Republic of China
*These authors contributed equally to this work
Correspondence: Haibin Lu, Email luhaibin@jlu.edu.cn
Abstract: Proteolysis Targeting Chimeras (PROTACs) have been extensively explored for the targeted degradation of disease-associated proteins due to their therapeutic ability to modulate proteins that are difficult to target by conventional small molecules, showing vast potential in treating refractory diseases such as cancer and neurodegenerative disorders. However, the clinical application of PROTACs is limited by their large molecular weight, low solubility, poor permeability, and the “hook effect”. Fortunately, the rapid advancement of nanotechnology offers new strategies to overcome some of the key challenges faced by traditional PROTAC technologies, potentially facilitating their clinical translation. In this review, we outline the mechanisms of action of PROTACs and explore their potential clinical significance, along with the main challenges in delivering these compounds. Additionally, we comprehensively summarize recent advancements in nanotechnology for enhancing the delivery efficiency of PROTAC drugs and discuss the limitations of current strategies and future perspectives. In conclusion, this review aims to deepen researchers’ understanding of this strategy, thereby advancing the clinical translation of PROTAC drugs and providing more effective strategies for treating complex, refractory diseases.
Keywords: PROTACs, nanotechnology, clinical application