Nano-PROTACs: state of the art and perspectives
PROteolysis TArgeting Chimeras (PROTACs), as a recently identified technique in the field of new drug development, provide new concepts for disease treatment and are expected to revolutionize drug discovery. With high specificity and flexibility, PROTACs serve as an innovative research tool to targe...
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| Published in | Nanoscale Vol. 16; no. 9; pp. 4378 - 4391 |
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| Main Authors | , , , , |
| Format | Journal Article |
| Language | English |
| Published |
England
Royal Society of Chemistry
29.02.2024
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| Subjects | |
| Online Access | Get full text |
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| Summary: | PROteolysis TArgeting Chimeras (PROTACs), as a recently identified technique in the field of new drug development, provide new concepts for disease treatment and are expected to revolutionize drug discovery. With high specificity and flexibility, PROTACs serve as an innovative research tool to target and degrade disease-relevant proteins that are not currently pharmaceutically vulnerable to eliminating their functions by hijacking the ubiquitin-proteasome system. To date, PROTACs still face the challenges of low solubility, poor permeability, off-target effects, and metabolic instability. The combination of nanotechnology and PROTACs has been explored to enhance the
in vivo
performance of PROTACs regarding overcoming these challenging hurdles. In this review, we summarize the latest advancements in the building-block design of PROTAC prodrug nanoparticles and provide an overview of existing/potential delivery systems and loading approaches for PROTAC drugs. Furthermore, we discuss the current status and prospects of the split-and-mix approach for PROTAC drug optimization. Additionally, the advantages and translational potentials of carrier-free nano-PROTACs and their combinational therapeutic effects are highlighted. This review aims to foster a deeper understanding of this rapidly evolving field and facilitate the progress of nano-PROTACs that will continue to push the boundaries of achieving selectivity and controlled release of PROTAC drugs.
Schematic illustration of the combinational strategy of nanotechnology and PROTACs (Nano-PROTACs): the typical shortcomings of traditional PROTACs and the nanotechnology-based strategies for PROTAC drugs optimization. |
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| Bibliography: | Jie Zhong received his Master of Science in Biophysics under the guidance of Prof. Xing-Jie Liang from the National Center for Nanoscience and Technology, Chinese Academy of Sciences. He is currently studying at the Faculty of Dentistry, The University of Hong Kong as a PhD candidate. The main aim of his activities is focused on the study of drug delivery, biomaterials, polymer self-assembly, and immunotherapy for the applications of cancer therapy and infection management. Yu-xiong Su received his Ph.D. degree from Sun-Yat Sen University, China. Currently, he works as a Professor and Division Chief in the Department of Oral and Maxillofacial Surgery, University of Hong Kong. Prof. Su is the lead surgeon for maxillofacial oncology and microsurgical reconstruction in the Department of Oral and Maxillofacial Surgery, Queen Mary Hospital, Hong Kong. He is actively involved in clinical and translational research. His main clinical and research interests include oral and maxillofacial oncology, computer-assisted surgery and 3D printing in head and neck reconstruction, salivary gland diseases and sialendoscopy. Ruiqi Zhao obtained her Master of Stomatological Medicine degree from Peking Union Medical College, Tsinghua University. Currently, she is a Ph.D. student at the Faculty of Dentistry, The University of Hong Kong, focusing on the diagnosis and treatment of oral and maxillofacial-head and neck tumors. Xinmiao Lan obtained a master degree from the Faculty of Dentistry, The University of Hong Kong in 2015 and a Ph.D. degree from the same faculty in September 2019. She finished her postdoctoral fellowship under the guidance of Prof. Richard Yu-xiong Su at the University of Hong Kong. Currently, she is an Associate Professor at Capital Medical University and an Honorary Associate Professor at the University of Hong Kong. Her research interests are nanoparticles, advanced nanomaterials, chemotherapy, immunotherapy, and cancer therapy. ObjectType-Article-2 SourceType-Scholarly Journals-1 ObjectType-Feature-3 content type line 23 ObjectType-Review-1 |
| ISSN: | 2040-3364 2040-3372 |
| DOI: | 10.1039/d3nr06059d |