Abstract: Nanomedicines (NMs) have played an increasing role in cancer therapy as carriers to efficiently deliver therapeutics into tumor cells. For this application, the uptake of NMs by tumor cells is usually a prerequisite to deliver the cargo to intracellular locations, which mainly relies on endocytosis. NMs can enter cells through a variety of endocytosis pathways. Different endocytosis pathways exhibit different intracellular trafficking routes and diverse subcellular localizations. Therefore, a comprehensive understanding of endocytosis mechanisms is necessary for increasing cellular entry efficiency and to trace the fate of NMs after internalization. This review focuses on endocytosis pathways of NMs in tumor cells, mainly including clathrin- and caveolae-mediated endocytosis pathways, involving effector molecules, expression difference of those molecules between normal and tumor cells, as well as the intracellular trafficking route of corresponding endocytosis vesicles. Then, the latest strategies for NMs to actively employ endocytosis are described, including improving tumor cellular uptake of NMs by receptor-mediated endocytosis, transporter-mediated endocytosis and enabling drug activity by changing intracellular routes. Finally, active targeting strategies towards intracellular organelles are also mentioned. This review will be helpful not only in explicating endocytosis and the trafficking process of NMs and elucidating anti-tumor mechanisms inside the cell but also in rendering new ideas for the design of highly efficacious and cancer-targeted NMs.

Keywords: nanomedicine, endocytosis pathway, clathrin, caveolae, endosome, organelle targeting


中文翻译：

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癌症治疗中纳米药物的内吞作用和细胞器靶向

摘要：纳米药物（NM）作为有效地将治疗药物递送至肿瘤细胞的载体，在癌症治疗中发挥着越来越重要的作用。对于该应用，肿瘤细胞摄取 NM 通常是将货物运送到细胞内位置的先决条件，这主要依赖于内吞作用。NMs可以通过多种内吞途径进入细胞。不同的内吞途径表现出不同的细胞内运输途径和不同的亚细胞定位。因此，全面了解内吞机制对于提高细胞进入效率和追踪 NM 内化后的命运是必要的。本综述重点关注肿瘤细胞中NM的内吞途径，主要包括网格蛋白和小窝介导的内吞途径，涉及效应分子、这些分子在正常细胞和肿瘤细胞之间的表达差异，以及相应内吞囊泡的细胞内运输途径。然后，描述了 NM 积极利用内吞作用的最新策略，包括通过受体介导的内吞作用、转运蛋白介导的内吞作用来改善肿瘤细胞对 NM 的摄取，以及通过改变细胞内途径来实现药物活性。最后，还提到了针对细胞内细胞器的主动靶向策略。本综述不仅有助于阐明 NM 的内吞作用和运输过程以及阐明细胞内的抗肿瘤机制，而且有助于为设计高效且针对癌症的 NM 提供新思路。

关键词:纳米医学, 内吞途径, 网格蛋白, 小凹, 内体, 细胞器靶向