Biodegradable Quantum Dot Nanocomposites Enable Live Cell Labeling and Imaging of Cytoplasmic Targets
Biodegradable Quantum Dot Nanocomposites Enable Live Cell Labeling and Imaging of Cytoplasmic Targets
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DOI：
10.1021/nl802311t
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发表时间：
2008-11-01
期刊：
影响因子：
10.8
通讯作者：
Chan, Warren C. W.
中科院分区：
文献类型：
--
作者：
Kim, Betty Y. S.;Jiang, Wen;Chan, Warren C. W.
半导体量子点（QDs）作为新一代的荧光探针，为生物过程的成像和研究提供了巨大的希望。尽管QD具有优异的上级光学性质，但由于可用的递送方法效率低、递送过程中细胞的状态或功能改变以及需要表面官能化的QD用于特异性标记亚细胞结构，因此用于活细胞监测和跟踪细胞质过程的QD仍然有限。在这里，我们提出了一种非侵入性的方法来成像亚细胞结构的活细胞使用生物共轭量子点纳米复合材料。通过在可生物降解的聚合物纳米球内掺入抗体包被的QD，我们设计了一种生物响应性递送系统，其通过纳米复合材料表面电荷极性的pH依赖性逆转经历内溶酶体到胞质的易位。在进入细胞溶质后，聚合物纳米球经历水解，从而释放QD生物缀合物。这种方法有利于活细胞内亚细胞结构的多重标记，而不需要细胞固定或膜透化。与常规的细胞内递送技术相比，这种方法允许QD的高通量细胞质递送，对细胞的毒性最小。更重要的是，这一发展展示了一个重要的合理的策略，为生物应用的多功能纳米系统的设计。
Semiconductor quantum dots (QDs) offer great promise as the new generation of fluorescent probes to image and study biological processes. Despite their superior optical properties, QDs for live cell monitoring and tracking of cytoplasmic processes remain limited due to inefficient delivery methods available, altered state or function of cells during the delivery process and the requirement of surface-functionalized QDs for specific labeling of subcellular structures. Here, we present a noninvasive method to image subcellular structures in live cells using bioconjugated QD nanocomposites. By incorporating antibody-coated QDs within biodegradable polymeric nanospheres, we have designed a bioresponsive delivery system that undergoes endolysosomal to cytosolic translocation via pH-dependent reversal of nanocomposite surface charge polarity. Upon entering the cytosol, the polymer nanospheres undergo hydrolysis thus releasing the QD bioconjugates. This approach facilitates multiplexed labeling of subcellular structures inside live cells without the requirement of cell fixation or membrane permeabilization. As compared to conventional intracellular delivery techniques, this approach allows the high throughput cytoplasmic delivery of QDs with minimal toxicity to the cell. More importantly, this development demonstrates an important rational strategy for the design of a multifunctional nanosystem for biological applications.