Research progress in the use of cationic carbon dots for the integration of cancer diagnosis with gene treatment
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摘要: 阳离子碳点(CCDs)是表面带正电荷的一类碳点(CDs)，可通过CDs和含氨基(—NH2)的阳离子化合物经“一步法”或“两步法”制备得到，既保留了CDs良好的荧光性能、低毒性及生物相容性，又提高了基因的负载输送能力及细胞摄取能力，使得CCDs在癌症靶向荧光成像和基因治疗领域中有重要的应用价值。本文综述了CCDs的制备方法和优异性能，说明CCDs可作为显像剂及基因的良好靶向载体；此外，还介绍了CCDs用于癌症诊治的基本原理及在癌症诊断和基因治疗方面的应用，并提出目前CCDs面临的问题及未来的发展趋势。Abstract: As a type of carbon dot (CD) with a positive charge on their surface, cationic carbon dots (CCDs) can be obtained from CDs and amino-containing cationic compounds by one-step or two-step preparation. They not only retain the good fluorescence performance, low toxicity and biocompatibility of CDs, but also improve their gene delivery efficiency and cell uptake capacity. These excellent properties give CCDs potential advantages in the fields of the targeted fluorescence imaging of cancers and gene therapy. This paper reviews the preparation methods and properties of CCDs, suggesting that they can be used as good targeting carriers for imaging cancer and gene therapy. In addition, the basic principles of CCDs for cancer detection and treatment, and their uses in integrated cancer diagnosis and gene therapy are introduced. Current problems and future development trends of CCDs for this purpose are discussed.
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Figure 1. The properties of CCDs and their application in cancer fluorescence imaging diagnosis and gene therapy.
Figure 4. CCDs show good photoluminescence and fluorescence stability[47] (Reprinted with permission by copyright © 2017 American Chemical Society).
Figure 5. Confocal fluorescence images of U-87 cells incubated with (a−c) 50 μg mL−1 GQDs, (d−f) PEI1800 GQDs, and (g−i) PEI600 GQDs for 18 h. (a), (d), and (g) are the fluorescence images of U-87 cells labeled with these three GQDs, with excitation at 405 nm. (b), (e), and (h) are the bright-field images of U-87 cells. (c), (f), and (i) are the merged images of U-87 cells incubated with three GQDs[54] (Reprinted with permission by copyright © 2017 American Chemical Society).
Figure 6. (a) A) the binding capacity of CCDs and siRNA with different nitrogen/phosphate (N/P) ratios was analyzed by agarose gel electrophoresis; B) the complex formed by CCDs and siRNA with 10 nitrogen/phosphate (N/P) ratio was added to different heparin quantities for heparin decomposition analysis, (b) A−C) in vivo optical imaging, A) control group, B) free siRNA, C) CCDs/siRNA complex, and D) quantitative analysis of luciferase gene expression in fluC-4T1 xenograft after injection of CCDs/siRNA complex and (c) A−C) in vivo optical imaging, and D) quantitative analysis of luciferase gene expression in 4T1 xenograft after injection of CCDs/pDNA complex[59] (Reprinted with permission by copyright © 2014 John Wiley and Sons Ltd).
Figure 8. (a) Diagrammatic drawing of CCDs/siRNA, (b) gene silencing effect of EGFR and Cyclin B1 after CCDs/pooled siRNA, CCDs/single siRNA and pooled siRNA were treated in lung cancer H460 cells for 12, 24 and 48 h, (c) A−C) fluorescence images of lung tumors before and after treatment, B) 7 days after administration, C) 10 days after administration, D) loaded siRNA complexes deposited in the lung area, E) control group[60] (Reprinted with permission by copyright © 2016 Springer Nature).
Figure 9. (a) Schematic diagram of CCDs, (b) confocal laser scanning microscope images of CCDs@siRNA and MGC-803 incubated for 2 h and 5 h, (c) apoptosis analysis of MGC-803 cells treated with CCDs@Survivin siRNA for 48 h. (1−3) are untreated group, sham transfection group and negative control group, (4−6) are Survivin siRNA-3, Survivin siRNA-2 and Survivin siRNA-1[58] (Reprinted with permission by copyright © 2014 BioMed Central).
Table 1. Summary of CCDs prepared by the one-step methods.
Method Carbon source Zeta
(mV)QY
(%)Size
(nm)Fluorescent color Ref. Microwave Glucose, Arginine +21.8±0.2 12.7 1−7 Blue [32] glycerol, PEI +24 9.4 <50 Blue [33] Pyrolysis Spermidine +45 3.85 6.33±1.35 Blue [34] Hydrothermal Malic acid, PEI +26 41 1.2−5.1 Green [35] Cetrimonium bromide +10 20 1−2.5 Blue [36] 
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Table 2. Summary of CCDs prepared by the two-step methods.
Method Carbon source Zeta (mV) QY (%) Size (nm) Fluorescent color Ref. Amide reaction CA, Urea, bPEI +24 18.7 10 Blue [37] CA, EDA, bPEI +46.68±
0.78- 22.8±6.7 Blue [38] Electrostatic attraction Candle soot, PEI +40 - <8.1 - [39] CA, EDA, PEI +15.6 - 122.7 Blue [40]
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