Cationic Ag2S NIR Quantum Dots and Their Theranostic Applications

Introduction: Luminescent semiconductor quantum dot research in the field of medicine and biotechnology is moving towards those with emission in the near-infrared in order to improve the penetration depth and reduce... [ view full abstract ]

Introduction: Luminescent semiconductor quantum dot research in the field of medicine and biotechnology is moving towards those with emission in the near-infrared in order to improve the penetration depth and reduce scattering and autofluorescence of the natural tissue. QD industry and research is moving towards Cd, Pb and Hg free compositions for both visible and NIR QDs. In such a new era of QD research, Ag2S NIR QDs emerged as a new and one of the most promising compositions. We have developed several cationic Ag2S NIR QDs with strong emission in NIR I region as new theranostic nanoparticles. Synthesis of such particles with PEI containing coating, particle properties and their efficiency in gene transfection, drug delivery and combination therapy coupled with strong luminescence allowing optical detection will be discussed.

Methods: Nanoparticles were synthesized in aqueous solutions of silver salt with a thiol source such as Na2S or TAA in the presence of PEI (branched or linear; 25kDa) and 2-mercaptopropionic acid (2MPA) or L-cysteine (Cys). Reactions were run at different temperatures and pH. Folic acid tagged PEG with a carboxylic acid end group was conjugated with EDC/NHS to cationic QDs in some formulations. GFP and P53 were loaded to QDs at different N/P ratios. Doxorubicin (Dox) was loaded from PBS.

Results and Discussions: Stable colloidal cationic QDs were obtained with PEI/2MPA and with PEI/Cys mixed coating using both linear and branched PEI.  QDs with quantum yield as high as 150% (with respect to LDS dye) were obtained.  Strong intracellular signal indicated great potential as an imaging tool. Transfection of GFP and P53 to cells demonstrate their efficiency as theranostic nanoparticles. P53/Dox combination was also loaded to some formulations and achieved improved cytotoxicity in P53 knockdown cells. FA-PEG conjugated compositions were loaded with Dox and selectively delivered drug to folate receptor overexpressed HeLa cells in high efficiency.

Overall a portfolio of cationic Ag2S and their theranostic use will be discussed.