Self-Oxygenating PROTAC Microneedle for Spatiotemporally-Confined Protein Degradation and Enhanced Glioblastoma Therapy
文献类型：期刊论文
| 作者 | Jiang, Xingyu8; Lai, Yi1,2; Xia, Wenzheng1,7; Yang, Wenfang1,5; Wang, Junjue1,5; Pan, Jiaxing1,2; Zhao, Qian2; Zhou, Feng2; Li, Shiqin1,2; Zhang, Shunan8 |
| 刊名 | ADVANCED MATERIALS
 |
| 出版日期 | 2025-03-03 |
| 页码 | 13 |
| 关键词 | acid-activatable photodynamic therapy double-layered microneedle glioblastoma therapy light-activatable PROTAC prodrug protein degradation |
| ISSN号 | 0935-9648 |
| DOI | 10.1002/adma.202411869 |
| 通讯作者 | Xu, Zhiai(zaxu@chem.ecnu.edu.cn) |
| 英文摘要 | Glioblastoma (GBM) is the most aggressive subtype of primary brain tumors, which marginally respond to standard chemotherapy due to the blood-brain barrier (BBB) and the low tumor specificity of the therapeutics. Herein, a double-layered microneedle (MN) patch is rationally engineered by integrating acid and light dual-activatable PROteolysis TArgeting Chimera (PROTAC) nanoparticles and self-oxygenating BSA-MnO2 (BM) nanoparticles for GBM treatment. The MN is administrated at the tumor site to locally deliver the PROTAC prodrug and BM nanoparticles. The PROTAC nanoparticles are rapidly released from the outer layer of the MN and specifically activated in the acidic intracellular environment of tumor cells. Subsequently, near-infrared light activates the photosensitizer to produce singlet oxygen (O-1(2)) through photodynamic therapy (PDT), thereby triggering spatiotemporally-tunable degradation of bromodomain and extraterminal protein 4 (BRD4). The BM nanoparticles, in the inner layer of the MN, serve as an oxygen supply station, and counteracts tumor hypoxia by converting hydrogen peroxide (H2O2) into oxygen (O-2), thus promoting PDT and PROTAC activation. This PROTAC prodrug-integrated MN significantly inhibits tumor growth in both subcutaneous and orthotopic GBM tumor models. This study describes the first spatiotemporally-tunable protein degradation strategy for highly efficient GBM therapy, potentially advancing precise therapy of other kinds of refractory brain tumors. |
| WOS关键词 | TUMOR ; MAINTENANCE ; EFFICACY ; HYPOXIA ; GLIOMA |
| 资助项目 | National Natural Science Foundation of China ; Science and Technology Commission of Shanghai Municipality[23490712700] ; Science and Technology Commission of Shanghai Municipality[20430711800] ; Science and Technology Commission of Shanghai Municipality[23ZR1475000] ; Shanghai Institute of Materia Medica, Chinese Academy of Sciences ; [22474042] ; [82203041] ; [U22A20328] ; [W2412035NSFC-FWO] |
| WOS研究方向 | Chemistry ; Science & Technology - Other Topics ; Materials Science ; Physics |
| 语种 | 英语 |
| WOS记录号 | WOS:001435668200001 |
| 出版者 | WILEY-V C H VERLAG GMBH |
| 源URL | [http://119.78.100.183/handle/2S10ELR8/316454]  |
| 专题 | 中国科学院上海药物研究所 |
| 通讯作者 | Xu, Zhiai |
| 作者单位 | 1.Shanghai Inst Mat Med, Chinese Acad Sci, Ctr Pharmaceut, Shanghai 201203, Peoples R China 2.Chinese Acad Sci, Shanghai Inst Mat Med, State Key Lab Chem Biol, Shanghai 201203, Peoples R China 3.Shenzhen Bay Lab, Inst Syst & Phys Biol, Shenzhen 518067, Peoples R China 4.Shenzhen Bay Lab, Inst Biomed Hlth Technol & Engn, Shenzhen 518067, Peoples R China 5.Nanjing Univ Chinese Med, Sch Chinese Mat Med, Nanjing 210023, Peoples R China 6.Capital Med Univ, Beijing Tiantan Hosp, Dept Neurosurg, Beijing 100070, Peoples R China 7.Shanghai Jiao Tong Univ, Shanghai Peoples Hosp 9, Sch Med, Dept Plast & Reconstruct Surg, Shanghai 200011, Peoples R China 8.East China Normal Univ, Sch Chem & Mol Engn, Shanghai 200241, Peoples R China |
| 推荐引用方式 GB/T 7714 | Jiang, Xingyu,Lai, Yi,Xia, Wenzheng,et al. Self-Oxygenating PROTAC Microneedle for Spatiotemporally-Confined Protein Degradation and Enhanced Glioblastoma Therapy[J]. ADVANCED MATERIALS,2025:13. |
| APA | Jiang, Xingyu.,Lai, Yi.,Xia, Wenzheng.,Yang, Wenfang.,Wang, Junjue.,...&Xu, Zhiai.(2025).Self-Oxygenating PROTAC Microneedle for Spatiotemporally-Confined Protein Degradation and Enhanced Glioblastoma Therapy.ADVANCED MATERIALS,13. |
| MLA | Jiang, Xingyu,et al."Self-Oxygenating PROTAC Microneedle for Spatiotemporally-Confined Protein Degradation and Enhanced Glioblastoma Therapy".ADVANCED MATERIALS (2025):13. |
入库方式： OAI收割
来源：上海药物研究所
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