Exploring the synthesis and biomedical applications of biocompatible quantum dots (QDs) is currently one of the fastest growing fields of nanotechnology. Hence, in this work, we present a facile approach to produce water-soluble (cadmium-free) quaternary Zn-Ag-In-S (ZAIS) QDs. Their efficient photoluminescence (PL) emissions can be tuned widely in the range of 525-625 nm by controlling the size and composition of the QDs with the PL quantum yields (QYs) of 15-30%. These highly luminescent ZAIS QDs are less toxic due to the absence of highly toxic cadmium, and can be versatilely modified by a DHLA-PEG-based ligand. Importantly, after being modified by tumor cell-specific targeting ligands (e.g., folate and RGD peptide), the PEGylated quaternary QDs show potential applications in tumor cell imaging as a promising alternative for Cd-based QDs.

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Supplementary data are available at Bioinformatics online.

Exploring the synthesis of new biocompatible quantum dots (QDs) helps in overcoming the intrinsic toxicity of the existing QDs composed of highly toxic heavy metals (e.g., Cd, Hg, Pb, etc.) and is particularly interesting for the future practical application of QDs in biomedical imaging. Hence, in this report, a new one-pot approach to oil-soluble (highly toxic heavy metal-free) highly luminescent quaternary Zn-Ag-In-Se (ZAISe) QDs was designed. Their photoluminescence (PL) emission could be systematically tuned from 660 to 800 nm by controlling the Ag/Zn feed ratio, and their highest PL quantum yield is close to 50% after detailed optimization. Next, by using biodegradable RGD peptide (arginine-glycine-aspartic acid)-modified N-succinyl-N'-octyl-chitosan (RGD-SOC) micelles as a water transfer agent, the versatility of these quaternary ZAISe QDs for multiscale bioimaging of micelles (namely, in vitro and in vivo evaluating the tumor targeting of drug carriers) was further explored, as a promising alternative for Cd- and Pb-based QDs.

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