Citation: Du Fangkai, Xu Jiangsheng, Zeng Fang, Wu Shuizhu. Preparation of a Multifunctional Nano-carrier System Based on Carbon Dots with pH-Triggered Drug Release[J]. Acta Chimica Sinica, ;2016, 74(3): 241-250. doi: 10.6023/A15120780 shu

Preparation of a Multifunctional Nano-carrier System Based on Carbon Dots with pH-Triggered Drug Release

  • Corresponding author: Du Fangkai, dufangkai501@163.com Wu Shuizhu, shzhwu@scut.edu.cn
  • Received Date: 15 December 2015

    Fund Project: the National Key Basic Research Program of China 2013CB834702NSFC 21474031, 21174040, 21025415China Postdoctoral Science Foundation 2015M572305

Figures(11)

  • A folated-functionalized nano-carrier system based on carbon dots was successfully synthesized for cancer cell-targeted drug delivery. In this report, using microwave-assisted assay the fluorescent CDots could be obtained via microwave-assisted pyrolysis of glycerol in the presence of 4,7,10-trioxa-1,13-tridecanediamine. The particle size of the CDots was confirmed by AFM and HR-TEM. The finding showed that the average diameter of CDots is about 4 nm. Incorporating (via a cleavable bond) an anticancer drug, which was Doxorubicin (DOX) in this study, and a targeting ligand (folic acid) onto carbon dot produces a more specific anticancer prodrug DOX-CDots-FA. The structure of the DOX-CDots-FA was characterized by 1H NMR and UV-vis analysis. The loading content of DOX was determined by UV-vis analysis to be 13.5 wt%, and the content of the targeting ligand FA was calculated as 3.13 wt% based on 1H NMR measurement. Particle size parameter of DOX-CDots-FA was determined by HR-TEM. The results showed that the average diameter of DOX-CDots-FA is about 6 nm. In addition, DOX-CDots-FA showed pH-dependent release, that is, the drug releases faster in pH=5.2 buffer solution than in pH=7.4 one. The cytotoxicity of DOX-CDots-FA, DOX-CDots nanoparticles and free DOX were evaluated and compared using HeLa and L929 cell lines. For the FR-positive HeLa cells, DOX-CDots-FA nanoparticles exhibit superior cytotoxicity as compared to DOX-CDots nanoparticles. These results showed that the FA moieties in DOX-CDots-FA nanoparticles play an important role in enhancing the cytotoxic effect as they increase the binding to FR-expressing cells. This high affinity binding subsequently increases their intracellular uptake as a result of receptor-mediated endocytosis. The FA molecules present on the surface of the nanoparticle prodrug do not have a remarkable effect on cellular uptake and/or cytotoxicity for FR-negative L929 cell lines. The confocal microscope studies revealed that FA-conjugated prodrug DOX-CDots-FA exhibited higher cellular uptake than FA-free nanosystem DOX-CDots which also led to higher cytotoxicity. Thus, multifunctional nano-carrier system could be a promising nanosize anticancer drug carrier with excellent targeting property.
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