Optimized Lipid Nanoparticles for Co-Delivery of mRNA and siRNA Therapeutics in Refractory Liver Cancer
文献类型：期刊论文
| 作者 | Liao, Yuqin3,4,5,6; Zeng, Xiaodong3,4,5; Zhang, Xinwei2,3,4,5; Hu, Yukun1,3,4,5,6; Zhao, Yicheng1,3,4,5,6; Luo, Qiusi1,3,4,5,6; Ren, Chunlin3,4,5,7,8; Zhou, Haibing6; Hong, Xuechuan3,4,5,6,7,8; Xiao, Yuling3,4,5,6 |
| 刊名 | ADVANCED MATERIALS
 |
| 出版日期 | 2026-01-09 |
| 页码 | 14 |
| 关键词 | co-delivery ferroptosis hepatocellular carcinoma machine learning sorafenib-resistant |
| ISSN号 | 0935-9648 |
| DOI | 10.1002/adma.202519473 |
| 英文摘要 | Hepatocellular carcinoma (HCC) exhibits poor prognosis and rapid resistance to sorafenib, particularly involving p53 loss and Nrf2 hyperactivation. Here, we employ machine learning (ML)-assisted structure-activity relationship (SAR) analysis to guide the engineering of a library of 120 degradable ionizable lipids, enabling the rational design of fluorinated aromatic lipid nanoparticles (LNPs) optimized for combinatorial RNA delivery. ML-based feature-importance analysis prioritizes -CF3 aromatic tails, and molecular dynamics simulations confirm that these tails enhance RNA binding and nanoparticle stability. The resulting A2T5-s LNPs, functionalized with lactobionic acid for selective HCC targeting, enable efficient co-delivery of p53 mRNA and Nrf2 siRNA. This strategy restores ferroptosis and induces apoptosis in sorafenib-resistant HCC by suppressing SLC7A11, leading to marked tumor inhibition. Our study demonstrates an ML-assisted LNP optimization strategy, advancing precision RNA therapeutics to overcome resistance in refractory liver cancer. |
| WOS关键词 | HEPATOCELLULAR-CARCINOMA ; FERROPTOSIS ; VIVO ; GENE |
| 资助项目 | NSFC Key International (Regional) Joint Research Program[W2511012] ; National Key R&D Program of China[2023YFC3605500] ; NSFC-BMGF Joint Project on Diagnostics RD[82561128253] ; National Natural Science Foundation of China[22477129] ; National Natural Science Foundation of China[82273796] ; Shenzhen Science and Technology Research[JCYJ20230807090100002] ; Shenzhen Science and Technology Research[JCYJ20240813111300001] ; Guangdong Basic and Applied Basic Research Foundation[2023A1515012649] ; Taishan Scholar Project of Shandong Province[TSQN202306320] ; Special Supporting Funds for Leading Talents at or above the Provincial Level in Yantai ; Tibet Autonomous Region Science and Technology Plan Project Key Project[XZ202301ZY0014G] ; Science and Technology Planning Project of Lhasa[LSKJ202445] ; Shandong Laboratory Program ; Natural Science Foundation of Shandong Province[ZR2023MB085] ; Natural Science Foundation of Shandong Province[ZR2024QH253] ; Natural Science Foundation of Yantai City ; [SYS202205] ; [ZR2025Q006] |
| WOS研究方向 | Chemistry ; Science & Technology - Other Topics ; Materials Science ; Physics |
| 语种 | 英语 |
| WOS记录号 | WOS:001657013600001 |
| 出版者 | WILEY-V C H VERLAG GMBH |
| 源URL | [http://119.78.100.183/handle/2S10ELR8/322563]  |
| 专题 | 国家级研究中心_原创新药研究全国重点实验室 |
| 通讯作者 | Xiao, Yuling |
| 作者单位 | 1.Wuhan Univ, Shenzhen Inst, Shenzhen, Peoples R China 2.Shandong Second Med Univ, Sch Pharm, Weifang, Peoples R China 3.Bohai Rim Adv Res Inst Drug Discovery, Shandong Lab Yantai Drug Discovery, Yantai, Peoples R China 4.Chinese Acad Sci, Shanghai Inst Mat Med, Ctr Pharmaceut, Shanghai, Peoples R China 5.Chinese Acad Sci, State Key Lab Drug Res, Shanghai, Peoples R China 6.Wuhan Univ, Zhongnan Hosp, Sch Pharmaceut Sci, Dept Radiol, Wuhan, Peoples R China 7.Fudan Univ, Natl Key Lab Adv Drug Formulat Overcoming Delivery, Shanghai, Peoples R China 8.Fudan Univ, Sch Pharmaceut Sci, Shanghai, Peoples R China |
| 推荐引用方式 GB/T 7714 | Liao, Yuqin,Zeng, Xiaodong,Zhang, Xinwei,et al. Optimized Lipid Nanoparticles for Co-Delivery of mRNA and siRNA Therapeutics in Refractory Liver Cancer[J]. ADVANCED MATERIALS,2026:14. |
| APA | Liao, Yuqin.,Zeng, Xiaodong.,Zhang, Xinwei.,Hu, Yukun.,Zhao, Yicheng.,...&Xiao, Yuling.(2026).Optimized Lipid Nanoparticles for Co-Delivery of mRNA and siRNA Therapeutics in Refractory Liver Cancer.ADVANCED MATERIALS,14. |
| MLA | Liao, Yuqin,et al."Optimized Lipid Nanoparticles for Co-Delivery of mRNA and siRNA Therapeutics in Refractory Liver Cancer".ADVANCED MATERIALS (2026):14. |
入库方式： OAI收割
来源：上海药物研究所
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