Modular Bioorthogonal Lipid Nanoparticle Modification Platforms for Cardiac Homing.
Modular Bioorthogonal Lipid Nanoparticle Modification Platforms for Cardiac Homing.
复制标题
用于心脏归巢的模块化生物正交脂质纳米颗粒修饰平台
DOI：
10.1021/jacs.3c07811
复制
发表时间：
2023-10-18
影响因子：
15
通讯作者：
Perriman, Adam W.
中科院分区：
文献类型：
--
作者：
Cruz-Samperio, Raquel;Hicks, Corrigan L.;Scott, Aaron;Gispert Contamina, Ignacio;Elani, Yuval;Richardson, Rebecca J.;Perriman, Adam W.
脂质纳米颗粒（LNP）正被广泛采用作为用于递送治疗有效载荷的载体，但通常缺乏内在的组织归巢性质。这些细胞外囊泡（EV）模拟物可以通过其脂质头基的电荷修饰靶向肝、肺或脾。归巢到其他组织仅通过使用小分子配体、肽或单克隆抗体的共价表面修饰策略实现，这些方法与大规模制造相结合具有挑战性。在此，我们设计了一种新的模块化人工膜结合蛋白（AMBP）平台，用于修饰LNPs后形成。该系统是由两个蛋白质模块，可以很容易地耦合使用生物正交化学产生的AMBP。第一种是膜锚模块，其包含与动态聚合物表面活性剂冠静电缀合的增压绿色荧光蛋白（scGFP）。第二个是包含来自细菌粘附素CshA的心脏组织纤连蛋白归巢序列的功能模块。我们证明，使用AMBP修饰的LNP表现出20倍的增加，在静态条件下，富含纤连蛋白的C2C12细胞的摄取和10倍的增加，在生理相关的剪切应力下，没有损失的细胞活力。此外，我们显示了AMBP修饰的LNP在斑马鱼心脏中的靶向定位，突出了它们作为治疗心脏疾病的载体的治疗潜力，更普遍地说，作为智能载体。
Lipid nanoparticles (LNPs) are becoming widely adopted as vectors for the delivery of therapeutic payloads but generally lack intrinsic tissue-homing properties. These extracellular vesicle (EV) mimetics can be targeted toward the liver, lung, or spleen via charge modification of their lipid headgroups. Homing to other tissues has only been achieved via covalent surface modification strategies using small-molecule ligands, peptides, or monoclonal antibodies—methods that are challenging to couple with large-scale manufacturing. Herein, we design a novel modular artificial membrane-binding protein (AMBP) platform for the modification of LNPs postformation. The system is composed of two protein modules that can be readily coupled using bioorthogonal chemistry to yield the AMBP. The first is a membrane anchor module comprising a supercharged green fluorescent protein (scGFP) electrostatically conjugated to a dynamic polymer surfactant corona. The second is a functional module containing a cardiac tissue fibronectin homing sequence from the bacterial adhesin CshA. We demonstrate that LNPs modified using the AMBP exhibit a 20-fold increase in uptake by fibronectin-rich C2C12 cells under static conditions and a 10-fold increase under physiologically relevant shear stresses, with no loss of cell viability. Moreover, we show targeted localization of the AMBP-modified LNPs in zebrafish hearts, highlighting their therapeutic potential as a vector for the treatment of cardiac disease and, more generally, as a smart vector.
登录
查看更多内容
DOI：
10.1038/s41578-021-00358-0
发表时间：
2021
期刊：
Nature reviews. Materials
影响因子：
--
作者：
Hou X;Zaks T;Langer R;Dong Y
通讯作者：
Dong Y
影响因子：
3.4
作者：
Ju C;Li Y;Shen Y;Liu Y;Cai J;Liu N;Ma G;Tang Y
通讯作者：
Tang Y
影响因子：
4.6
作者：
Balu R;Knott R;Cowieson NP;Elvin CM;Hill AJ;Choudhury NR;Dutta NK
通讯作者：
Dutta NK
影响因子：
39.3
作者：
Gallet, Romain;Dawkins, James;Marban, Eduardo
通讯作者：
Marban, Eduardo
影响因子：
15
作者：
Larsen, Jannik;Hatzakis, Nikos S.;Stamou, Dimitrios
通讯作者：
Stamou, Dimitrios