Ag2S/PEI teranostik nanoparçacıkların geliştirilmesi

In this study, biocompatible, heavy metal free and cationic Ag2S quantum dots (QDs) which luminesce in the medical range (700-900 nm) were synthesized with a mixed coating comprised of a small thiolated molecule such as 2-mercaptopropionic acid (2MPA) or L-Cyseine (Cys) and linear polyethyleneimine (PEI) at 2.5kDa and 25kDa molecular weights, instead of the branched 25kDa PEI, which is the golden standard for gene delivery, since it is less toxic. QDs coated with only linear PEI do not luminesce. However, QDs with the mixed coating, benefit from a synergy and are more luminescent than the 2MPA coated Ag2S which is known as one of the best luminescent Ag2S QDs in the literature. Quantum yield of 2MPA/PEI coated Ag2S QD (2MPA/PEI (2.5kDa): 20/80) is 310 % with respect to LDS 798 NIR dye. This is the highest quantum yield reported till today. Although a significant reduction in the luminescence intensity is observed over time, even after 8 months, the luminescence intensity is still quite high. Optical imaging studies of these QDs with HeLa cell line and C.elegans model organisms showed that these QDs can be strong optical labels and can be successfully used in optical imaging. In this study, the effect of pH during and after the reaction was also investigated. The strongest luminescence was detected in an acidic (pH 5) and the weakest luminescence was seen in basic environment (pH 10). Changes in the pH did not cause any shift in the emission wavelength of the 2MPA/PEI coated QDs but Cys/PEI coated QDs experienced a shift towards longer wavelengths at acidic pH. In vitro cytotoxicity of these cationic Ag2S QDs were determined in HeLa, HCT116 (p53-) and HCT116WT cells. Overall, 2MPA/PEI coated quantum dots are less toxic than Cys/PEI coated ones and the onset of toxicity is 7.5 µg/mL Ag dose. Significantly toxic dose of Cys/PEI coated Ag2S QDs is 7.5 µg/mL Ag in HeLa, 1.8 µg/mL Ag in HCT116WT and 18 µg/mL Ag in HCT116(p53-) cells. These doses are sufficient to test these particles in drug delivery and medical imaging studies. In addition, the intracellular uptake of the QDs were determined and correlated with the toxicity data. Effect of particle size and surface charge on the intracellular uptake was also investigated. Overall, strongly luminescent, cationic Ag2S NIR QDs were successfully prepared with the mixed coating comprised of L-PEI/2MPA and L-PEI/Cys at both low and high molecular weights. QDs are small in size and colloidally stable, which is crucial for any in vivo application. They have been demonstrated as strong optical probes for medical imaging.