Gambogic Acid Combined With CdTe QDs For Leukemia Cancer Cells Inhibition and Their Bio-Safety For Rat Brain
Authors: Xu Peipei , Chen Baoan , Li Jingyuan , Wang Xuemei 
Published: October 2019

Abstract
The development of new anticancer agents typically involves long research cycles, high cost and low efficiency and so on. There has been a growing public interest in the use of complementary and alternative medicine for cancer treatment and drug discovery. The emergence of nanotechnology and nanomaterials has greatly stimulated research in drug delivery and optimization. As a good fluorescence probe and simultaneously as potential drug carrier, Cadmium-Tellurium quantum dots (CdTe QDs) can optimize the use and a new potential therapy method of some drug-active compounds. Based on these considerations, we have explored the possibility to connect cysteamine (Cys) modified CdTe QDs (Cys-CdTe) to gambogic acid (GA). These functional QDs were studied for multi-functional drug delivery to investigate the synergetic effect of these composites between GA and QDs for human leukemia caner cells K562 and their drug-resistant cell line K562/A02 in vitro. Also the neurotoxicity of different drug systems for Sprague Dawley (SD) rat brain was analyzed by in vivo real-time microdialysis. The nanocomposites of GA loaded CdTe QDs were prepared and the drug releasing of GA-CdTe nanocomposites was performed at the medium of pH 6.0 and 7.4 in vitro. The cytotoxicity of GA and the nanocomposites for K562 and K562/A02 cells was studied by MTT, cell morphology, and flow cytometry. The labeling and imaging of CdTe QDs and the nanocomposites for cancer cells was performed by laser confocal fluorescence microscopy. Different drug systems were respectively injected into SD rat by vena caudalis and cerebrospinal fluid was collected by microdialysis in vivo. The neurotoxicity of different drug systems for rat brain was investigated by the changes of amino acid content in the cerebrospinal fluid. The Cys modified CdTe QDs showed the good fluorescence characteristics, with the wide excitation spectrum and narrow emission spectrum. The CdTe QDs could label in human leukemia cancer cells not only for K562 but also K562/A02 , which had the potential application in the cell imaging. Following the electrostatic attraction, surface adsorption et al, these CdTe QDs had the good capability of drug delivery with the high drug-loading and envelopment capacity. Also these GA-CdTe nanocomposites showed the pH sensitivity for the drug release and improved the drug's un-dissolvability. The GA-CdTe nanocomposites also had the fluorescence characteristics for labeling the different kinds of leukemia cancer cells. Gambogic acid play an important role in cancer therapy and also showed the sensitivity for the multidrug resistance (MDR) of K562/A02 cells in this study. The results indicated that GA-CdTe nanocomposites could significantly enhance the drug accumulation to improve the cytotoxicity and considerably overcome the multidrug resistance. GA-CdTe nanocomposites induced the arrest of G0/G1 phase to promote the cells apoptosis. The combination between GA and CdTe QDs can optimize the new potential therapeutic method for GA with the real time labeling and tracing during the disease therapy. The neurotoxicity of GA and GA-CdTe nanocomposites for rat brain was firstly explored by using the microdialysis in vivo. The results indicated that GA had the serious neurotoxicity through the concentration changes of amino acids for the rat brain. The concentration of some excitatory amino acids was remarkably increased. For the GA-CdTe nanocomposites based on CdTe QDs, the side effect of GA was visibly cut down, and the time to cause the neurotoxicity was apparently shortened. These nanocomposites own the better biocompatibility and bio-safety for the relevant cancer treatment in vitro and in vivo. This raises the promising possibility of the application of these fluorescent nanocomposites based on CdTe QDs for the target cancer therapy. The combination of GA with Cys-CdTe QDs can optimize the use and new potential multi-mode therapy of cancers. This may shed new light to exploit the potential application of the active compounds from Traditional Chinese Medicine (TCM).

Disclosures:
No relevant conflicts of interest to declare.