Water Transfer of Oil-Soluble ZnAgInSe/ZnS Quantum Dots by DHLA-PEG-Suc-cRGD Ligands for Tumor Targeted Bio-Imaging.

Semiconductor quantum dots have attracted increasing attention, owing to their unique optical and electrical properties compared to traditional organic fluorescent dyes. However, one of the main obstacles impeding their biological applications is their biocompatibility. Hence, in this work, for achieving biocompatible quantum dots, oil-soluble ZnAgInSe/ZnS quantum dots without highly toxic heavy metals were selected, and four kinds of biocompatible thiols (dihydrolipoic acid, L-cysteine, N-acetyl-L-cysteine and glutathione) were explored as their water transfer agents. Among them, dihydrolipoic acid was found to be more favorable for achieving strongly fluorescent water-soluble quantum dots. Based on this observation, a tumor targeted ligand, namely dihydrolipoic acid-poly(ethylene glycol)-succinic anhydride-cyclic arginine-glycine-aspartate, was designed to further enhance their tumor targeting ability. By means of in vitro cell and in vivo mice experiments, dihydrolipoic acid-poly(ethylene glycol)-succinic anhydride-cyclic arginine-glycine-aspartate stabilized ZnAgInSe/ZnS quantum dots were confirmed to have a high affinity for alpha(nu)beta(3) integrin receptor-positive U87MG tumor. This study demonstrates the versatility of highly fluorescent, broadly emissive ZnAgInSe/ZnS quantum dots for multi-scale biomedical optical imaging.