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Nanoparticle entry into cells; the cell biology weak link
Advanced Drug Delivery Reviews ( IF 16.1 ) Pub Date : 2022-06-29 , DOI: 10.1016/j.addr.2022.114403
Gareth Griffiths 1 , Jean Gruenberg 2 , Mark Marsh 3 , Jens Wohlmann 1 , Arwyn T Jones 4 , Robert G Parton 5
Affiliation  

Nanoparticles (NP) are attractive options for the therapeutic delivery of active pharmaceutical drugs, proteins and nucleic acids into cells, tissues and organs. Research into the development and application of NP most often starts with a diverse group of scientists, including chemists, bioengineers and material and pharmaceutical scientists, who design, fabricate and characterize NP in vitro (Stage 1). The next step (Stage 2) generally investigates cell toxicity as well as the processes by which NP bind, are internalized and deliver their cargo to appropriate model tissue culture cells. Subsequently, in Stage 3, selected NP are tested in animal systems, mostly mouse. Whereas the chemistry-based development and analysis in Stage 1 is increasingly sophisticated, the investigations in Stage 2 are not what could be regarded as 'state-of-the-art' for the cell biology field and the quality of research into NP interactions with cells is often sub-standard. In this review we describe our current understanding of the mechanisms by which particles gain entry into mammalian cells via endocytosis. We summarize the most important areas for concern, highlight some of the most common mis-conceptions, and identify areas where NP scientists could engage with trained cell biologists. Our survey of the different mechanisms of uptake into cells makes us suspect that claims for roles for caveolae, as well as macropinocytosis, in NP uptake into cells have been exaggerated, whereas phagocytosis has been under-appreciated.



中文翻译:

纳米粒子进入细胞;细胞生物学薄弱环节

纳米颗粒 (NP) 是将活性药物、蛋白质和核酸输送到细胞、组织和器官中的有吸引力的选择。对 NP 的开发和应用的研究通常始于各种各样的科学家,包括化学家、生物工程师以及材料和药物科学家,他们在体外设计、制造和表征NP(阶段1)。下一步(第 2 阶段)通常研究细胞毒性以及 NP 结合、内化并将其货物输送到适当的模型组织培养细胞的过程。随后,在第 3 阶段,选定的 NP 在动物系统(主要是小鼠)中进行测试。尽管第 1 阶段基于化学的开发和分析越来越复杂,但第 2 阶段的研究不能被视为细胞生物学领域的“最先进”和 NP 相互作用研究的质量电池通常不合标准。在这篇综述中,我们描述了我们目前对颗粒通过内吞作用进入哺乳动物细胞的机制的理解。我们总结了最重要的关注领域,强调了一些最常见的误解,并确定 NP 科学家可以与训练有素的细胞生物学家合作的领域。我们对摄入细胞的不同机制的调查使我们怀疑,关于小窝和巨胞饮作用在 NP 摄入细胞中的作用的说法被夸大了,而吞噬作用则被低估了。

更新日期:2022-06-29
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