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首页> 外文会议>Colloidal quantum dots for biomedical applications V >Delivery of Quantum Dot Bioconjugates to the Cellular Cytosol: Release from the endolysosomal system
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Delivery of Quantum Dot Bioconjugates to the Cellular Cytosol: Release from the endolysosomal system

机译：量子点生物共轭物传递到细胞质：从溶酶体系统释放。

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To realize their full potential as intracellular imaging and sensing reagents, robust and efficient methods for the targeted cellular delivery of luminescent semiconductor quantum dots (QDs) must be developed. We have previously shown that QDs decorated with histidine-terminated polyarginine cell-penetrating peptides (CPP) arc rapidly and specifically internalized via endocytosis by several mammalian cell lines with no cytotoxicity. Here we demonstrate the long-term intracellular stability and fate of these QD-peptide conjugates. We found that the QD-peptide conjugates remain sequestered within endolysosomal vesicles for up to three days after delivery. However, the CPP appeared to remain stably associated with the QD within these acidic vesicles over this time period. Hence, we explored a number of techniques to either actively deliver QDs directly to the cytosol or to facilitate the cndosomal release of endocytoscd QDs to the cytosol. Active methods (e.g., electroporation) delivered only modest amounts of QDs to the cytosol that appeared to form aggregates. Delivery of QDs using polymer-based transfection reagents resulted primarily in the endosomal sequestration of the QDs, although one commercial polymer tested delivered QDs to the cytosol but only after several days in culture and with a considerable degree of polymer-induced toxicity. Finally, a modular, amphiphilic peptide containing functionalities designed for cell penetration and vesicular membrane interaction demonstrated the ability to deliver QDs in a well-dispersed manner to the cytosol. This peptide mediated rapid QD uptake followed by a slower efficient endosomal release of the QDs to the cytosol that peaked at 48 hours post-delivery. Importantly, this QD-peptide conjugate elicited minimal cytotoxicity in two cell lines tested. A more detailed understanding of the mechanism of the peptide's uptake and endosomal escape attributes will lead to the design of further QD conjugates for targeted imaging and sensing applications.
机译：为了实现其作为细胞内成像和传感试剂的全部潜力，必须开发出用于靶向细胞递送发光半导体量子点（QD）的强大而有效的方法。先前我们已经证明，用组氨酸终止的聚精氨酸穿透细胞的肽（CPP）修饰的QD迅速且特异性地通过内吞作用被数种没有细胞毒性的哺乳动物细胞系内化。在这里，我们证明了这些QD肽结合物的长期细胞内稳定性和命运。我们发现，QD-肽共轭物在分娩后长达三天的时间内仍被隔离在溶酶体囊泡中。但是，在这段时间内，这些酸性囊泡中的CPP似乎与QD保持稳定关联。因此，我们探索了许多技术来将QD主动直接传递到细胞质中，或促进内吞CDD的染色体释放到细胞质中。主动方法（例如电穿孔）仅将适量的QD传递至似乎形成聚集体的胞质溶胶。使用一种基于聚合物的转染试剂的QD递送主要导致QD的内体隔离，尽管一种测试的商业聚合物将QD递送到了细胞质中，但仅在培养数天后才发生，并且具有相当程度的聚合物诱导的毒性。最后，包含用于细胞渗透和囊泡膜相互作用的功能性的模块化两亲肽展示了以良好分散的方式将QD传递至细胞质的能力。该肽介导了快速的QD摄取，随后是QD缓慢有效的内体释放到细胞质中，这种释放在分娩后48小时达到峰值。重要的是，这种QD肽共轭物在两种测试的细胞系中引起最小的细胞毒性。对肽摄取和内体逃逸属性的机理的更详细的了解将导致针对靶向成像和传感应用的其他QD缀合物的设计。

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