Bridging the In Vitro to In Vivo gap: Using the Chick Embryo Model to Accelerate Nanoparticle Validation and Qualification for In Vivo studies.
Bridging the In Vitro to In Vivo gap: Using the Chick Embryo Model to Accelerate Nanoparticle Validation and Qualification for In Vivo studies.
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DOI：
10.1021/acsnano.2c03990
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发表时间：
2022-12-27
期刊：
影响因子：
17.1
通讯作者：
Leong, Hon Sing
中科院分区：
文献类型：
--
作者：
Butler, Kimberly S.;Brinker, C. Jeffrey;Leong, Hon Sing
关键词：
我们假设，用于治疗应用的纳米颗粒（NP）在很大程度上没有实现其临床潜力，由于整体无法使用体外结果来预测NP在体内的性能。禽胚胎和相关的绒毛尿囊膜（CAM）已经成为体内临床前模型，其桥接体外和体内之间的差距，使得能够在生理相关条件下快速筛选NP行为，并提供快速、可获得、经济且更符合伦理的方法来鉴定用于体内使用的纳米颗粒。CAM是高度血管化的，并且模拟用作纳米颗粒捕获器的肝、脾和肺的发散/会聚脉管系统。注射到CAM脉管系统中的荧光标记的NP的活体成像使得能够在用微脉管系统灌注的任何感兴趣的组织中以单个NP尺度立即评估和量化纳米生物相互作用。在这篇综述中，我们强调了如何利用禽胚胎及其CAM作为临床前模型，以了解NP在血液和组织中的稳定性，外渗，生物相容性和NP随时间的分布，从而用于鉴定具有所需稳定性和性能的NP子集，以引入啮齿动物模型，并使结构的开发成为可能，属性关系和NP优化，而无需牺牲大量小鼠或其他啮齿动物。然后，我们回顾了鸡胚胎和CAM模型系统如何通过允许靶向（主动）和非靶向（被动）NP结合，内化和货物递送到单个细胞（与白血病和转移性癌症的治疗相关）和细胞系综（例如，用于癌症肿瘤的治疗或成像的感兴趣的癌症异种移植物）。最后，我们展示了新兴的技术，利用CAM在未来的纳米生物研究。
We postulate that nanoparticles (NPs) for use in therapeutic applications have largely not realized their clinical potential due to an overall inability to use in vitro results to predict NP performance in vivo. The avian embryo and associated chorioallantoic membrane (CAM) has emerged as an in vivo preclinical model that bridges the gap between in vitro and in vivo, enabling rapid screening of NP behavior under physiologically relevant conditions and providing a rapid, accessible, economical, and more ethical means of qualifying nanoparticles for in vivo use. The CAM is highly vascularized and mimics the diverging/converging vasculature of the liver, spleen, and lungs that serve as nanoparticle traps. Intravital imaging of fluorescently labeled NPs injected into the CAM vasculature enables immediate assessment and quantification of nano-bio interactions at the individual NP scale in any tissue of interest that is perfused with a microvasculature. In this review, we highlight how utilization of the avian embryo and its CAM as a preclinical model can be used to understand NP stability in blood and tissues, extravasation, biocompatibility, and NP distribution over time, thereby serving to identify a subset of NPs with the requisite stability and performance to introduce into rodent models and enabling the development of structure–property relationships and NP optimization without the sacrifice of large populations of mice or other rodents. We then review how the chicken embryo and CAM model systems have been used to accelerate the development of NP delivery and imaging agents by allowing direct visualization of targeted (active) and nontargeted (passive) NP binding, internalization, and cargo delivery to individual cells (of relevance for the treatment of leukemia and metastatic cancer) and cellular ensembles (e.g., cancer xenografts of interest for treatment or imaging of cancer tumors). We conclude by showcasing emerging techniques for the utilization of the CAM in future nano-bio studies.
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影响因子：
16.6
作者：
Ballantyne M;Woodcock M;Doddamani D;Hu T;Taylor L;Hawken RJ;McGrew MJ
通讯作者：
McGrew MJ
影响因子：
17.1
作者：
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影响因子：
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通讯作者：
Mak, T. W.
影响因子：
5.8
作者：
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通讯作者：
Ricci, Maurizio
影响因子：
3.2
作者：
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