In vitro and In vivo imaging using quantum dots
Our group can synthesize very bright CdSe/CdZnS quantum dots (100% efficiency: see Snee et al. J. Phys. Chem. C. 2011, 115, 19578), as well as several cadmium free systems. As discussed in the other research sections, we are developing new methods for water solubilizing QDs and for functionalizing them to make biological sensors or to remove non-specific interactions. Once we create a novel fluorescent quantum dot biological imaging agent, we then demonstrate the efficacy of its use in a biological system. We work with experts in biological imaging in these endeavors. Shown here are two recent breakthroughs:
1. Cell penetration using dentin phosphophoryn (DPP)-functional CdSe/CdZnS quantum dots in collaboration with the group of Anne George at UIC. As recently published by Rivindran et al. (J. Bio. Chem. 2013, 288, 16098), we have coated QDs with a dentin protein that allows for cytocellular delivery of live cells with quantum dots. The protein was fused with a nuclear localizing fragment to deliver QDs to the cell nucleus as shown on the left. Here you see red-emitting QDs in the nucleus of MC3T3 cells; the green emission is from endosomal markers. This work was surprising as it is well-known that cytocellular delivery of quantum dots into live cells is very difficult. This has been attempted several times using cationic ligands to coat the QDs, which subsequently get trapped into endosomes when exposed to cells. However, the endosomes rarely mature which leaves the dots trapped in them, which is unfortunate as endosomal staining is not of significant scientific interest.
In vivo imaging was also performed using these quantum dot-protein complexes in cells that were embedded inside of biomimetic scaffolds. Shown here is QD emission that was observed after two weeks from implantation.
We are still collaborating with the George group to simplify the delivery design.
2. Imaging studies with the group of Stephen Kron at the University of Chicago (Shamirian et al. J. Mat. Chem B 2015, 3, 8188). In this work we synthesized NIR-emitting cadmium free AgInS2/ZnS QDs and water solubilized them using several methods. The dots were then functionalized with PEG and used to image the mammary tumors in a BALB-neuT mouse. We hope that these imaging agents will be useful for assessing the efficacy of various cancer therapies.