Gao Xiaoling, Wang Tao, Wu Bingxian, Chen Jun, Chen Jiyao, Yue Yang, Dai Ning, Chen Hongzhuan, Jiang Xinguo
Department of Pharmaceutics, School of Pharmacy, Fudan University, Shanghai, PR China.
Biochem Biophys Res Commun. 2008 Dec 5;377(1):35-40. doi: 10.1016/j.bbrc.2008.09.077. Epub 2008 Sep 25.
Successful drug delivery by functionalized nanocarriers largely depends on their efficient intracellular transport which has not yet been fully understood. We developed a new tracking technique by encapsulating quantum dots into the core of wheat germ agglutinin-conjugated nanoparticles (WGA-NP) to track cellular transport of functionalized nanocarriers. The resulting nanoparticles showed no changes in particle size, zeta potential or biobinding activity, and the loaded probe presented excellent photostability and tracking ability. Taking advantage of these properties, cellular transport profiles of WGA-NP in Caco-2 cells was demonstrated. The cellular uptake begins with binding of WGA to its receptor at the cell surface. The subsequent endocytosis happened in a cytoskeleton-dependent manner and by means of clathrin and caveolae-mediated mechanisms. After endosome creating, transport occurs to both trans-Golgi and lysosome. Our study provides new evidences for quantum dots as a cellular tracking probe of nanocarriers and helps understand intracellular transport profile of lectin-functionalized nanoparticles.
功能化纳米载体的成功药物递送很大程度上取决于其高效的细胞内转运，而这一点尚未完全了解。我们通过将量子点封装到小麦胚芽凝集素缀合纳米颗粒（WGA-NP）的核心中，开发了一种新的追踪技术，以追踪功能化纳米载体的细胞转运。所得纳米颗粒在粒径、zeta电位或生物结合活性方面没有变化，并且负载的探针具有出色的光稳定性和追踪能力。利用这些特性，展示了WGA-NP在Caco-2细胞中的细胞转运概况。细胞摄取始于WGA与其在细胞表面的受体结合。随后的内吞作用以细胞骨架依赖的方式发生，并通过网格蛋白和小窝介导的机制进行。在内体形成后，转运发生至反式高尔基体和溶酶体。我们的研究为量子点作为纳米载体的细胞追踪探针提供了新证据，并有助于了解凝集素功能化纳米颗粒的细胞内转运概况。
