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首页> 外文期刊>Integrative Biology: quantitative biosciences from nano to macro >Delivering quantum dot-peptide bioconjugates to the cellular cytosol: escaping from the endolysosomal system
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Delivering quantum dot-peptide bioconjugates to the cellular cytosol: escaping from the endolysosomal system

机译：将量子点肽生物结合物递送至细胞质：从溶酶体系统逃逸

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摘要

For luminescent quantum dots (QDs) to realize their full potential as intracellular labeling, imaging and sensing reagents, robust noninvasive methods for their delivery to the cellular cytosol must be developed. Our aim in this study was to explore a range of methods aimed at delivering QDs to the cytosol. We have previously shown that QDs functionalized with a polyarginine 'Tat' cell-penetrating peptide (CPP) could be specifically delivered to cells via endocytic uptake with no adverse effects on cellular proliferation. We began by assessing the long-term intracellular fate and stability of these QD-peptide conjugates. We found that the QDs remained sequestered within acidic endolysosomal vesicles for at least three days after initial uptake while the CPP appeared to remain stably associated with the QD throughout this time. We next explored techniques designed to either actively deliver QDs directly to the cytosol or to combine endocytosis with subsequent endosomal escape to the cytosol in several eukaryotic cell lines. Active delivery methods such as electroporation and nucleofection delivered only modest amounts of QDs to the cytosol as aggregates. Delivery of QDs using a variety of transfection polymers also resulted in primarily endosomal sequestration of QDs. However, in one case the commercial PULSin (TM) reagent did facilitate a modest cytosolic dispersal of QDs, but only after several days in culture and with significant polymer-induced cytotoxicity. Finally, we demonstrated that an amphiphilic peptide designed to mediate cell penetration and vesicle membrane interactions could mediate rapid QD uptake by endocytosis followed by a slower efficient endosomal release which peaked at 48 h after initial delivery. Importantly, this QD-peptide bioconjugate elicited minimal cytotoxicity in the cell lines tested.
机译：为了使发光量子点（QD）充分发挥其作为细胞内标记，成像和传感试剂的潜力，必须开发出可靠的非侵入性方法将其递送到细胞质中。我们在这项研究中的目的是探索一系列旨在将QD传递至细胞质的方法。先前我们已经证明，用聚精氨酸“ Tat”细胞穿透肽（CPP）功能化的QD可以通过内吞摄取特异性地传递到细胞，而对细胞增殖没有不利影响。我们从评估这些QD肽结合物的长期细胞内命运和稳定性开始。我们发现，QDs在最初摄入后至少三天仍被隔离在酸性溶酶体囊泡中，而CPP在整个这段时间内似乎仍与QD稳定相关。接下来，我们探索了旨在主动将QD直接传递到细胞质中或将内吞作用与随后的内体逸出结合到几种真核细胞系中的细胞质中的技术。主动递送方法（例如电穿孔和核转染）仅将适量的QD作为聚集体递送至胞质溶胶。使用多种转染聚合物递送QD，也主要导致了QD的内体隔离。然而，在一种情况下，市售PULSin TM试剂确实促进了QD的适度的胞质分散，但仅在培养数天后并且具有明显的聚合物诱导的细胞毒性。最后，我们证明了设计用于介导细胞渗透和囊泡膜相互作用的两亲性肽可以介导内吞作用快速QD摄取，随后是较慢的有效内体释放，该释放在初始递送后48小时达到峰值。重要的是，这种QD肽生物共轭物在测试的细胞系中引起最小的细胞毒性。

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