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首页> 外文期刊>Philosophical Transactions of the Royal Society of London, Series B. Biological Sciences >Using macropinocytosis for intracellular delivery of therapeutic nucleic acids to tumour cells
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Using macropinocytosis for intracellular delivery of therapeutic nucleic acids to tumour cells

机译:使用Macropinocytosis用于细胞内递送治疗性核酸至肿瘤细胞

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摘要

Nucleic acids are a rapidly emerging therapeutic modality with the potential to become the third major drug modality alongside antibodies and small molecules. Owing to the unfavourable physico-chemical characteristics of nucleic acids, such as large size and negative charge, intracellular delivery remains a fundamental challenge to realizing this potential. Delivery technologies such as lipids, polymers and peptides have been used to facilitate delivery, with many of the most successful technologies using macropinocytosis to gain cellular entry; mostly by default rather than design. Fundamental knowledge of macropinocytosis is rapidly growing, presenting opportunities to better tailor design strategies to target this pathway. Furthermore, certain types of tumour cells have been observed to have high levels of macropinocytic activity and traffic cargo to favourable destinations within the cell for endosomal release, providing unique opportunities to further use this entry route for drug delivery. In this article, we review the delivery systems reported to be taken up by macropinocytosis and what is known about the mechanisms for regulating macropinocytosis in tumour cells. From this analysis, we identify new opportunities for exploiting this pathway for the intracellular delivery of nucleic acids to tumour cells.
机译:核酸是一种迅速出现的治疗方式,其潜力使抗体和小分子沿着抗体和小分子成为第三种主要药物模态。由于核酸的不利物理化学特性,例如大尺寸和负电荷,细胞内递送仍然是实现这一潜力的根本挑战。脂质,聚合物和肽等递送技术已被用于促进递送,其中许多使用Macropinocytosis的最多的技术获得细胞入口;主要是默认而不是设计。宏观细胞症的基本知识正在迅速增长,提出了更好地定制设计策略来瞄准这条路的机会。此外,已经观察到某些类型的肿瘤细胞在细胞内具有高水平的大磷细胞活性和交通货物,用于内体释放的细胞内,为进一步使用该进入途径进行药物递送,提供独特的机会。在本文中,我们审查报告的递送系统被癌细胞增多症造成,以及关于调节肿瘤细胞中癌细胞增生症的机制的认识。从该分析来看,我们确定新的机会,用于利用这种途径以使核酸细胞内递送到肿瘤细胞。

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