Humanized Biomimetic Nanovesicles for Neuron Targeting.
Humanized Biomimetic Nanovesicles for Neuron Targeting.
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DOI：
10.1002/advs.202101437
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发表时间：
2021-10
期刊：
影响因子：
--
通讯作者：
Krencik R
中科院分区：
文献类型：
--
作者：
Zinger A;Cvetkovic C;Sushnitha M;Naoi T;Baudo G;Anderson M;Shetty A;Basu N;Covello J;Tasciotti E;Amit M;Xie T;Taraballi F;Krencik R
纳米囊泡 (NV) 正在成为货物运输的创新治疗诊断工具。最近，用来自特定细胞类型的膜蛋白对 NV 进行表面工程已被证明可以提高 NV 的生物相容性并实现功能属性的整合。然而，这种类型的仿生方法尚未在神经系统中使用人类神经细胞进行探索。在这里，本文通过整合来自人类多能干细胞衍生神经元的膜蛋白，优化并验证了两种类型的神经元靶向 NV 的可扩展和可重复生产，每种 NV 都具有适合潜在治疗货物的独特脂质配方骨架。结果表明，内源性和基因工程细胞衍生的蛋白质均能有效转移至 NV，而不会破坏其理化特性。与裸 NV 相比，具有神经元衍生膜蛋白的 NV 表现出增强的神经元关联和摄取。 3D 神经球培养物的活力不会受到治疗的破坏，这验证了基于类器官的方法作为 NV 测试平台的实用性。最后，这些结果证实了仿生人源化 NV 与啮齿动物脑神经内神经元的细胞关联和摄取。总之，这里报告的可定制 NV 可实现旨在促进神经再生的下一代功能化治疗诊断学。从人类多能干细胞或分化的神经元中提取膜蛋白，并与脂质结合以合成仿生纳米囊泡（NV）。 NV 的神经靶向可以使用单层培养物和 3D 类器官在体外进行评估，也可以通过将 NV 直接注射到小鼠三叉神经节中进行体内评估。
Nanovesicles (NVs) are emerging as innovative, theranostic tools for cargo delivery. Recently, surface engineering of NVs with membrane proteins from specific cell types has been shown to improve the biocompatibility of NVs and enable the integration of functional attributes. However, this type of biomimetic approach has not yet been explored using human neural cells for applications within the nervous system. Here, this paper optimizes and validates the scalable and reproducible production of two types of neuron‐targeting NVs, each with a distinct lipid formulation backbone suited to potential therapeutic cargo, by integrating membrane proteins that are unbiasedly sourced from human pluripotent stem‐cell‐derived neurons. The results establish that both endogenous and genetically engineered cell‐derived proteins effectively transfer to NVs without disruption of their physicochemical properties. NVs with neuron‐derived membrane proteins exhibit enhanced neuronal association and uptake compared to bare NVs. Viability of 3D neural sphere cultures is not disrupted by treatment, which verifies the utility of organoid‐based approaches as NV testing platforms. Finally, these results confirm cellular association and uptake of the biomimetic humanized NVs to neurons within rodent cranial nerves. In summary, the customizable NVs reported here enable next‐generation functionalized theranostics aimed to promote neuroregeneration. Membrane proteins are extracted from either human pluripotent stem cells or differentiated neurons and combined with lipids to synthesize biomimetic nanovesicles (NVs). Neural targeting of NVs can be evaluated both in vitro using monolayer cultures and 3D organoids and in vivo by direct injection of NVs into murine trigeminal ganglions.
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DOI：
10.1016/j.apsb.2016.02.001
发表时间：
2016-07
期刊：
Acta pharmaceutica Sinica. B
影响因子：
--
作者：
Ha D;Yang N;Nadithe V
通讯作者：
Nadithe V
启动纳米颗粒引导的诊断和对人体器官微生物生理系统的疗法。
影响因子：
11.7
作者：
Choi JH;Lee J;Shin W;Choi JW;Kim HJ
通讯作者：
Kim HJ
影响因子：
3.9
作者：
Genc, Ruekan;Clergeaud, Gael;O'Sullivan, Ciara K.
通讯作者：
O'Sullivan, Ciara K.
影响因子：
14.8
作者：
Dekkers, Johanna F.;Alieva, Maria;Rios, Anne C.
通讯作者：
Rios, Anne C.
系统的三维共培养迅速概括了人类神经元与星形胶质细胞之间的相互作用。
影响因子：
5.9
作者：
Krencik R;Seo K;van Asperen JV;Basu N;Cvetkovic C;Barlas S;Chen R;Ludwig C;Wang C;Ward ME;Gan L;Horner PJ;Rowitch DH;Ullian EM
通讯作者：
Ullian EM