Proton-resistant quantum dots: Stability in gastrointestinal fluids and implications for oral delivery of nanoparticle agents

Semiconductor quantum dots (QDs) have shown great promise as fluorescent probes for molecular, cellular and in vivo imaging. However, the fluorescence of traditional polymer-encapsulated QDs is often quenched by proton-induced etching in acidic environments. This is a major problem for applications of QDs in the gastrointestinal tract because the gastric (stomach) environment is strongly acidic (pH 1–2). Here we report the use of proton-resistant surface coatings to stabilize QD fluorescence under acidic conditions. Using both hyperbranched polyethylenimine (PEI) and its polyethylene glycol derivative (PEG-grafted PEI), we show that the fluorescence of core shell CdSe /CdS/ ZnS QDs is effectively protected from quenching in simulated gastric fluids. In comparison, amphiphilic lipid or polymer coatings provide no protection under similarly acidic conditions. The proton-resistant QDs are found to cause moderate membrane damage to cultured epithelial cells, but PEGylation (PEG grafting) can be used to reduce cellular toxicity and to improve nanoparticle stability. [Figure not available: see fulltext.]