PROTAC Prodrug-Integrated Nanosensitizer for Potentiating Radiation Therapy of Cancer
文献类型：期刊论文
| 作者 | Zhang, Shunan3,4,5; Lai, Yi3,4; Pan, Jiaxing2,3,4; Saeed, Madiha3,4; Li, Shiqin3,4; Zhou, Huiling3,4,5; Jiang, Xingyu3,4,5; Gao, Jing3,4; Zhu, Yun1; Yu, Haijun3,4
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| 刊名 | ADVANCED MATERIALS
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| 出版日期 | 2024-02-22 |
| 页码 | 12 |
| ISSN号 | 0935-9648 |
| 关键词 | active tumor targeting nanosensitizer PROTAC prodrug radiation therapy tumor microenvironment |
| DOI | 10.1002/adma.202314132 |
| 通讯作者 | Yu, Haijun(hjyu@simm.ac.cn) ; Zhang, Wen(wzhang@chem.ecnu.edu.cn) ; Xu, Zhiai(zaxu@chem.ecnu.edu.cn) |
| 英文摘要 | Radiation therapy (RT) is one of the primary options for clinical cancer therapy, in particular advanced head and neck squamous cell carcinoma (HNSCC). Herein, the crucial role of bromodomain-containing protein 4 (BRD4)-RAD51 associated protein 1 (RAD51AP1) axis in sensitizing RT of HNSCC is revealed. A versatile nanosensitizer (RPB7H) is thus innovatively engineered by integrating a PROteolysis TArgeting Chimeras (PROTAC) prodrug (BPA771) and hafnium dioxide (HfO2) nanoparticles to downregulate BRD4-RAD51AP1 pathway and sensitize HNSCC tumor to RT. Upon intravenous administration, the RPB7H nanoparticles selectively accumulate at the tumor tissue and internalize into tumor cells by recognizing neuropilin-1 overexpressed in the tumor mass. HfO2 nanoparticles enhance RT effectiveness by amplifying X-ray deposition, intensifying DNA damage, and boosting oxidative stress. Meanwhile, BPA771 can be activated by RT-induced H2O2 secretion to degrade BRD4 and inactivate RAD51AP1, thus impeding RT-induced DNA damage repair. This versatile nanosensitizer, combined with X-ray irradiation, effectively regresses HNSCC tumor growth in a mouse model. The findings introduce a PROTAC prodrug-based radiosensitization strategy by targeting the BRD4-RAD51AP1 axis, may offer a promising avenue to augment RT and more effective HNSCC therapy. The dual-loaded nanosensitizer, featuring PROTAC (PROteolysis TArgeting Chimeras) prodrug and HfO2 nanoparticles, is engineered to sensitize radiotherapy in head and neck cancer by amplifying DNA damage and inactivating RAD51-associated protein 1 through bromodomain protein 4 degradation. image |
| WOS关键词 | PROTEIN-DEGRADATION ; NANOPARTICLES ; LIGAND ; CELLS ; HEAD |
| 资助项目 | National Natural Science Foundation of China ; Science and Technology Commission of Shanghai Municipality[20430711800] ; Science and Technology Commission of Shanghai Municipality[23ZR1475000] ; China Postdoctoral Science Foundation[2021M700157] ; Shanghai Postdoctoral Excellence Program[2021424] ; China National Postdoctoral Program for Innovative Talents[BX20220320] ; China National Postdoctoral Program for Innovative Talents[LG-QS-202206-04] ; State Key Laboratory of Chemical Biology ; Shanghai Institute of Materia Medica, Chinese Academy of Sciences[2021-09-YHJ-06] ; Shanghai ninth people's hospital[YBKA201905] ; Shanghai Jiao Tong University School of Medicine[Leica TCS SP8] ; [22074043] ; [82203041] ; [U22A20328] ; [22174047] |
| WOS研究方向 | Chemistry ; Science & Technology - Other Topics ; Materials Science ; Physics |
| 语种 | 英语 |
| 出版者 | WILEY-V C H VERLAG GMBH |
| WOS记录号 | WOS:001169516300001 |
| 源URL | [http://119.78.100.183/handle/2S10ELR8/309925]  |
| 专题 | 中国科学院上海药物研究所 |
| 通讯作者 | Yu, Haijun; Zhang, Wen; Xu, Zhiai |
| 作者单位 | 1.Shanghai Jiao Tong Univ, Peoples Hosp 9, Dept Oral & Maxillofacial Head & Neck Oncol, Sch Med, Shanghai 200011, Peoples R China 2.Shanghai Jiao Tong Univ, Xinhua Hosp, Sch Med, Dept Gastroenterol, Shanghai 2000092, Peoples R China 3.Chinese Acad Sci, Shanghai Inst Mat Med, Ctr Pharmaceut, Shanghai 201203, Peoples R China 4.Chinese Acad Sci, Shanghai Inst Mat Med, State Key Lab Chem Biol, Shanghai 201203, Peoples R China 5.East China Normal Univ, Sch Chem & Mol Engn, Shanghai 200241, Peoples R China |
| 推荐引用方式 GB/T 7714 | Zhang, Shunan,Lai, Yi,Pan, Jiaxing,et al. PROTAC Prodrug-Integrated Nanosensitizer for Potentiating Radiation Therapy of Cancer[J]. ADVANCED MATERIALS,2024:12. |
| APA | Zhang, Shunan.,Lai, Yi.,Pan, Jiaxing.,Saeed, Madiha.,Li, Shiqin.,...&Xu, Zhiai.(2024).PROTAC Prodrug-Integrated Nanosensitizer for Potentiating Radiation Therapy of Cancer.ADVANCED MATERIALS,12. |
| MLA | Zhang, Shunan,et al."PROTAC Prodrug-Integrated Nanosensitizer for Potentiating Radiation Therapy of Cancer".ADVANCED MATERIALS (2024):12. |
入库方式： OAI收割
来源：上海药物研究所
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