Ke Li¹, Qianwen Li², Rui Meng²

¹Pharmacy Department, union   Hospital, Tongji Medical College, Huazhong University of Science and Technology, ²Cancer Center, union   Hospital, Tongji Medical College, Huazhong University of Science and Technology.

Objective:Protein kinase CK2 is a ubiquitously expressed serine/threonine kinase which plays multiple roles in the regulation of gene expression and cell proliferation. Our previous studies have demonstrated that CK2 inhibitor (Quinalizarin) could dramatically enhance the radiosensitivity of human lung cancer cells: A549 and H460 cells under X ray irradiation. However, less specificity of Quinalizarin to tumor cells can also do harm to benign cells. In this study, to overcome this shortcoming, we developed a novel multifunctional nanocarrier based on gold nanoparticles (AuNPs) for drug delivery as well as tumor cell targeting and imaging. Method: Fifteen nm spherical AuNPs as the core of the nanocomplex were synthesized by Frens method. Through adding Quinalizarin and AuNPs in sequence into the sulfhydryl calcium acetate solution the reactions occurred. Sulfhydrylcalcium acetate was introduced here as a bridge to connect both AuNPs and Quinalizarin. The resulted nanocomplex were then characterised by TEM and zetasizer and further quantified by UV-Vis spectroscopic analysis. Based on the uniquemultiphoton absorption induced luminescence (MAIL) property of AuNPs, a novel approach named multiphoton imaging-UV/V is spectroscopic analysis (MIUSA) was applied here for simultaneous visualization and quantification of the Quinalizarin loaded nanocomplex during the cellular uptake process. Result: AuNPs showed spherical shape with good sizedistribution in an average diameter of 15±1.2 nm confirmed by TEM. Quinalizarin was completely conjugated to the surface of AuNPs indicated by color changes of the reaction solution from colorless to dark blue and finally to orange red (Fig1b). UV-Vis analysis showed the maximum absorption peak of 462 nm indicating successfully synthesis of quinalizarin loaded AuNPs which are clear and remaining stable for 1 week in room temperature. Multiphoton laser scanning microscopy images showed pronounced cellular uptake rate of the nanoparticles in A549 cells (Fig1c). This uptake process can be quantified by MIUSA approach. Conclusion: We provided promising strategies for targeted delivery of protein kinase CK2 inhibitor to lung cancer cells by virtue of nanotechnology. This will have a tremendous potential in lung cancer therapy.

Key Words: Protein Kinase CK2  Quinalizarin  Gold nanoparticles