机构：[1]State Key Laboratory of Chemical Oncogenomics, School of Chemical Biology and Biotechnology, Peking University Shenzhen Graduate School, Shenzhen 518055, China.[2]Pingshan Translational Medicine Center, Shenzhen Bay Laboratory, Shenzhen 518118, China.[3]Frontiers Medical Center, Tianfu Jincheng Laboratory, Chengdu 610212, Sichuan, China.[4]Department of Pharmacy, Department of Gastrointestinal Surgery, Shenzhen Second People's Hospital (Shenzhen Institute of Translational Medicine), Guangdong Key Laboratory for Biomedical Measurements and Ultrasound Imaging, National-Regional Key Technology Engineering Laboratory for Medical Ultrasound, School of Biomedical Engineering, Shenzhen University Medical School, Shenzhen 518060, China.深圳市第二人民医院深圳市康宁医院深圳医学信息中心
Proteolysis Targeting Chimera (PROTAC) technology represents a promising new approach for target protein degradation using a cellular ubiquitin-proteasome system. Recently, we developed a split-and-mix nanoplatform based on peptide self-assembly, which could serve as a self-adjustable platform for multifunctional applications. However, the lower drug efficacy limits further biomedical applications of peptide-based SM-PROTAC. In this study, we develop a novel split-and-mix PROTAC system based on liposome self-assembly (LipoSM-PROTAC), concurrent with modification of FA (folate) to enhance its tumor-targeting capabilities. Estrogen receptors (ERα) were chosen as the protein of interest (POI) to validate the efficacy of Lipo degraders. Results demonstrate that this PROTAC can be efficiently and selectively taken up into the cells by FA receptor-positive cells (FR+) and degrade the POI with significantly reduced concentration. Compared to the peptide-based SM-PROTACs, our designed LipoSM-PROTAC system could achieve therapeutic efficacy with a lower concentration and provide opportunities for clinical translational potential. Overall, the LipoSM-based platform shows a higher drug efficacy, which offers promising potential applications for PROTAC and other biomolecule regulations.
基金：
This work was funded by the National Key Research and
Development Program “Synthetic Biology” Key Special Project
of China, 2021YFC2103900, 2021YFA0910803; the Natural
Science Foundation of China grants 21977010; the National
Center for Biological Medicine Technology Innovation,
NCTIB2022HS01017; the Natural Science Foundation of
Guangdong P r o v i n c e , 2022A1515010996 and
2020A1515010766; Hospital Fund of Shenzhen People’s
Hospital, SYKYPY201909; Shenzhen Science and Technology P r o g r a m , R C J C 2 0 2 0 0 7 1 4 1 1 4 4 3 3 0 5 3 ,
JCYJ20200109140406047, JCYJ20220818095808019 and
JCYJ20210324102809026; the Beijing National Laboratory
of Molecular Science open grant BNLMS20160112 and
Shenzhen-Hong Kong Institute of Brain Science-Shenzhen
Fundamental Research Institutions grant 2019SHIBS0004.
This work is supported by the Proteomic Platform of Pingshan
translational medicine center, Shenzhen Bay Laboratory.
第一作者机构：[1]State Key Laboratory of Chemical Oncogenomics, School of Chemical Biology and Biotechnology, Peking University Shenzhen Graduate School, Shenzhen 518055, China.
共同第一作者：
通讯作者：
通讯机构：[1]State Key Laboratory of Chemical Oncogenomics, School of Chemical Biology and Biotechnology, Peking University Shenzhen Graduate School, Shenzhen 518055, China.[2]Pingshan Translational Medicine Center, Shenzhen Bay Laboratory, Shenzhen 518118, China.[3]Frontiers Medical Center, Tianfu Jincheng Laboratory, Chengdu 610212, Sichuan, China.
推荐引用方式(GB/T 7714)：
Song Chunli,Jiao Zijun,Hou Zhanfeng,et al.Selective Protein of Interest Degradation through the Split-and-Mix Liposome Proteolysis Targeting Chimera Approach[J].JOURNAL OF THE AMERICAN CHEMICAL SOCIETY.2023,145(40):21860-21870.doi:10.1021/jacs.3c05948.
APA：
Song Chunli,Jiao Zijun,Hou Zhanfeng,Wang Rui,Lian Chenshan...&Yin Feng.(2023).Selective Protein of Interest Degradation through the Split-and-Mix Liposome Proteolysis Targeting Chimera Approach.JOURNAL OF THE AMERICAN CHEMICAL SOCIETY,145,(40)
MLA：
Song Chunli,et al."Selective Protein of Interest Degradation through the Split-and-Mix Liposome Proteolysis Targeting Chimera Approach".JOURNAL OF THE AMERICAN CHEMICAL SOCIETY 145..40(2023):21860-21870
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