论文：Enhanced mRNA delivery using ultrasound-delivered click reactive anchors诗人：Emilio Di Ianni, Jueun Jeon, Huiyu Hu, Jeremy M. Quintana, Chanseo Lee, Edwina Abou Haidar, Sedra Mohammadi, Ayrton Zargani-Piccardi, Mohammed Mahamdeh, Iván Coto Hernández, Thomas S.C. Ng, Koen Breyne, Hakho Lee, Xandra O. Breakefield, Miles A. Miller参考文献联接：//www.biorxiv.org/content/10.1101/2025.01.28.635330v1.abstract结语：Therapeutic nucleic acid delivery has many potential applications, but it remains challenging to target extrahepatic tissues in a flexible and image-guided manner. To address this issue, we report a bioorthogonal pre-targeting strategy that uses focused ultrasound to promote the delivery of mRNA-loaded lipid nanoparticles (mRNA-LNP). We synthesized amphiphilic click reactive anchors (ACRAs) consisting of a phospholipid PEG-conjugate functionalized with transcyclooctene (TCO) or its companion reactive partner methyltetrazine (mTz), yielding ACRA-TCO and ACRA-mTz. ACRA derivatives were screened for cellular activity, yielding functionalized DOPE-PEG (1,2-dioleoyl-sn-glycero-3-phosphoethanolamine-N- (polyethylene glycol)) derivatives outperforming those containing saturated lipid or branched PEG. Nanobubbles encapsulating ultrasound-responsive gas precursor delivered ACRA-TCO to targeted cells and tissues using focused ultrasound, and this pre-targeting promoted the subsequent delivery of mRNA- LNP functionalized with companion ACRA-mTz. In cell cultures and in mice, ultrasound pre-targeting enhanced the accumulation of mTz-functionalized small molecule and nanoparticle compounds by 75% and 3.6-fold, respectively, and increased gene expression using mRNA-LNP in vivo. Taken together, this report presents a modular, ultrasound-enabled strategy for enhancing nucleic acid delivery in targeted tissues.

种生物学正交预靶向药物攻略 ，该攻略 灵活运用焦聚超声波增强载mRNA的脂质微米颗粒剂（mRNA-LNP）的递送。当我们炼制了两亲单击表现锚（ACRA），其由磷脂PEG共轭物主成，该共轭物用反式环辛烯（TCO）或其陪伴表现性配体甲基四嗪（mTz）用途化，然后转换成ACRA-TCO和ACRA-mTz。对ACRA并衍生物学来了肿瘤细胞渗透性建立，结果显示察觉效果化的DOPE-PEG（1,2-二油酰-sn-甘油-3-磷酸无水乙醇胺-N-（聚乙二醇））繁衍物的机械性能远远高于内含饱和状态脂质或支链PEG的繁衍物。nm汽泡快件多普勒彩超为了响应气味前体，再生利用专注多普勒彩超将ACRA-TCO递运至对方细胞核和安排，种预靶点的功效催进了己经递送经ACRA-mTz效果化的mRNA-LNP。在细胞核陪养物和小鼠身机体，高周波预靶点意义分別使mTz职能化的小原子核和nm小粒化学物质的积攒加快了75%和3.6倍，并加快了mRNA-LNP在身机体的DNA表明。经验经验，本意见书提供 了一大种信息实用化、高周波可以的方案，用到资料核酸在总体目标组织性中的递送。有关的安利：DSPE-PEG-ProgestroneDSPE-PEG-RGDDSPE-PEG-SCDSPE-PEG-SCMDSPE-PEG-SGDSPE-PEG-SHDSPE-PEG-SilaneDSPE-PEG-SP2-AADSPE-PEG-SSDSPE-PEG-TCODSPE-PEG-Tetrazine上述小文章相关内容原因各个期刊杂志或参考文献，如无知识产权侵权请认识我国删出！