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01 June 2009
Proton-Resistant Quantum Dots: Stability in Gastrointestinal Fluids and Implications for Oral Delivery of Nanoparticle Agents
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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.
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Proton-Resistant Quantum Dots: Stability in Gastrointestinal Fluids and Implications for Oral Delivery of Nanoparticle Agents
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Abstract
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.
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Acknowledgements
The work was partly supported by NIH Grants (P20 GM072069, R01 CA108468-01, U01 HL080711, and U54CA119338) and the Georgia Cancer Coalition Distinguished Cancer Scholars Program (to S. N.).
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