Cell-penetrating quantum dots based on multivalent and endosome-disrupting surface coatings
Cell-penetrating quantum dots based on multivalent and endosome-disrupting surface coatings
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DOI：
10.1021/ja068158s
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发表时间：
2007-03-21
影响因子：
15
通讯作者：
Nie, Shuming
中科院分区：
文献类型：
--
作者：
Duan, Hongwei;Nie, Shuming
我们报道了基于多价和内小体破坏(内溶)表面涂层的细胞穿透量子点(QD)的发展。超支化共聚物配体，如聚乙二醇接枝聚乙烯亚胺(PEI-g-PEG)，通过直接的配体交换反应包裹和溶解发光量子点。由于多价胺基团的正电荷和质子海绵效应，这类配体交换的量子点能够穿透细胞膜，也能够破坏活细胞的内体细胞器。接枝的聚乙二醇链段对于降低PEI的细胞毒性以及提高纳米粒子的整体稳定性和生物相容性是必不可少的。与以往用两亲性聚合物包裹的量子点相比，穿透细胞的量子点尺寸更小，在酸性环境中更稳定。细胞摄取和成像研究表明，每个PEI分子的聚乙二醇接枝数对内化量子点的细胞内途径有显著的影响。特别是，包裹了PEI-g-PEG(2)的量子点被内吞作用迅速内化，最初储存在小泡中，随后缓慢的内体逃逸和释放到细胞质中。这些见解对于设计和开发用于细胞内成像和治疗应用的纳米颗粒试剂非常重要。
We report the development of cell-penetrating quantum dots (QDs) based on the use of multivalent and endosome-disrupting (endosomolytic) surface coatings. Hyperbranched copolymer ligands such as polyethylene glycol (PEG) grafted polyethylenimine (PEI-g-PEG) are found to encapsulate and solubilize luminescent quantum dots through direct ligand-exchange reactions. Because of the positive charges and a "proton sponge effect" associated with multivalent amine groups, this class of ligand-exchanged QDs is able to penetrate cell membranes and is also able to disrupt endosomal organelles in living cells. The grafted PEG segment is essential for reducing the cytotoxicity of PEI as well as for improving the overall nanoparticle stability and biocompatibility. In comparison with previous QDs encapsulated with amphiphilic polymers, the cell-penetrating QDs are smaller in size and are considerably more stable in acidic environments. Cellular uptake and imaging studies reveal that the number of PEG grafts per PEI molecule has a pronounced effect on the intracellular pathways of internalized QDs. In particular, QDs coated with PEI-g-PEG(2) are rapidly internalized by endocytosis, and are initially stored in vesicles, followed by slow endosomal escape and release into the cytoplasm. These insights are important toward the design and development of nanoparticle agents for intracellular imaging and therapeutic applications.