Department of Materials Science and Engineering, Pohang University of Science and Technology (POSTECH), Pohang, Kyungbuk, Korea.
Biomacromolecules. 2012 Aug 13;13(8):2554-61. doi: 10.1021/bm300796q. Epub 2012 Jul 30.
Fluorescent nanosized carbon dots (Cdots) are an emerging bioimaging agent with excellent chemical inertness and marginal cytotoxicity in comparison to widely used semiconductor quantum dots. In this work, we report the application of Cdots for real time bioimaging of target specific delivery of hyaluronic acid (HA) derivatives. Polyethylene glycol (PEG) diamine-capped Cdots were synthesized by the pyrolysis of citric acid in a hot solvent. The synthesized Cdots showed strong fluorescence under UV excitation with emission properties dependending on the excitation wavelength. HA-Cdot conjugates were synthesized by amide bond formation between amine groups of Cdot and carboxylic groups of HA. After confirmation of the negligible cytotoxicity of Cdots and HA-Cdot conjugates, in vitro bioimaging was carried out for target specific intracellular delivery of the HA-Cdot conjugates by HA receptor-mediated endocytosis. Furthermore, in vivo real-time bioimaging of Cdots and HA-Cdot conjugates exhibited the target specific delivery of HA-Cdot conjugates to the liver with abundant HA receptors. Taken together, we could confirm the feasibility of HA derivatives as a target-specific drug delivery carrier for the treatment of liver diseases and Cdots as a promising bioimaging agent.
荧光纳米级碳点(Cdots)是一种新兴的生物成像剂,与广泛使用的半导体量子点相比,具有优异的化学惰性和微小的细胞毒性。在这项工作中,我们报告了 Cdots 在透明质酸(HA)衍生物的靶向特异性递送的实时生物成像中的应用。聚乙二醇(PEG)二胺封端的 Cdots 通过在热溶剂中柠檬酸的热解合成。合成的 Cdots 在紫外光激发下表现出强荧光,其发射性质取决于激发波长。通过 Cdots 上的氨基与 HA 的羧基之间的酰胺键形成将 HA-Cdot 缀合物合成。在证实 Cdots 和 HA-Cdot 缀合物的细胞毒性可以忽略不计后,通过 HA 受体介导的内吞作用进行了 HA-Cdot 缀合物的靶向特异性细胞内递送的体外生物成像。此外,体内实时生物成像显示了 HA-Cdot 缀合物在具有丰富 HA 受体的肝脏中的靶向递药。综上所述,我们可以确认 HA 衍生物作为治疗肝脏疾病的靶向药物递送载体的可行性,以及 Cdots 作为有前途的生物成像剂的可行性。