Aqueous Synthesis of PEGylated Quantum Dots with Increased Colloidal Stability and Reduced Cytotoxicity

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Original languageEnglish
Pages (from-to)414-426
Number of pages13
JournalBioconjugate chemistry
Volume27
Issue number2
Publication statusPublished - 14 Nov 2015

Abstract

Ligands used on the surface of colloidal nanoparticles (NPs) have a significant impact on physiochemical properties of NPs and their interaction in biological environments. In this study, we report a one-pot aqueous synthesis of 3-mercaptopropionic acid (MPA)-functionalized CdTe/CdS/ZnS quantum dots (Qdots) in the presence of thiol-terminated methoxy polyethylene glycol (mPEG) molecules as a surface coordinating ligand. The resulting mPEG-Qdots were characterized by using potential, FTIR, thermogravimetric (TG) analysis, and microscale thermophoresis (MST) studies. We investigated the effect of mPEG molecules and their grafting density on the Qdots photophysical properties, colloidal stability, protein binding affinity, and in vitro cellular toxicity. Moreover, cellular binding features of the resulting Qdots were examined by using three-dimensional (3D) tumor-like spheroids, and the results were discussed in detail. Promisingly, mPEG ligands were found to increase colloidal stability of Qdots, reduce adsorption of proteins to the Qdot surface, and mitigate Qdot-induced side effects to a great extent. Flow cytometry and confocal microscopy studies revealed that PEGylated Qdots exhibited distinctive cellular interactions with respect to their mPEG grafting density. As a result, mPEG molecules demonstrated a minimal effect on the ZnS shell deposition and the Qdot fluorescence efficiency at a low mPEG density, whereas they showed pronounced effect on Qdot colloidal stability, protein binding affinity, cytotoxicity, and nonspecific binding at a higher mPEG grafting amount.

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Aqueous Synthesis of PEGylated Quantum Dots with Increased Colloidal Stability and Reduced Cytotoxicity. / Ulusoy, Mehriban; Jonczyk, Rebecca; Walter, Johanna Gabriela et al.
In: Bioconjugate chemistry, Vol. 27, No. 2, 14.11.2015, p. 414-426.

Research output: Contribution to journalArticleResearchpeer review

Ulusoy M, Jonczyk R, Walter JG, Springer S, Lavrentieva A, Stahl F et al. Aqueous Synthesis of PEGylated Quantum Dots with Increased Colloidal Stability and Reduced Cytotoxicity. Bioconjugate chemistry. 2015 Nov 14;27(2):414-426. doi: 10.1021/acs.bioconjchem.5b00491
Ulusoy, Mehriban ; Jonczyk, Rebecca ; Walter, Johanna Gabriela et al. / Aqueous Synthesis of PEGylated Quantum Dots with Increased Colloidal Stability and Reduced Cytotoxicity. In: Bioconjugate chemistry. 2015 ; Vol. 27, No. 2. pp. 414-426.
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title = "Aqueous Synthesis of PEGylated Quantum Dots with Increased Colloidal Stability and Reduced Cytotoxicity",
abstract = "Ligands used on the surface of colloidal nanoparticles (NPs) have a significant impact on physiochemical properties of NPs and their interaction in biological environments. In this study, we report a one-pot aqueous synthesis of 3-mercaptopropionic acid (MPA)-functionalized CdTe/CdS/ZnS quantum dots (Qdots) in the presence of thiol-terminated methoxy polyethylene glycol (mPEG) molecules as a surface coordinating ligand. The resulting mPEG-Qdots were characterized by using potential, FTIR, thermogravimetric (TG) analysis, and microscale thermophoresis (MST) studies. We investigated the effect of mPEG molecules and their grafting density on the Qdots photophysical properties, colloidal stability, protein binding affinity, and in vitro cellular toxicity. Moreover, cellular binding features of the resulting Qdots were examined by using three-dimensional (3D) tumor-like spheroids, and the results were discussed in detail. Promisingly, mPEG ligands were found to increase colloidal stability of Qdots, reduce adsorption of proteins to the Qdot surface, and mitigate Qdot-induced side effects to a great extent. Flow cytometry and confocal microscopy studies revealed that PEGylated Qdots exhibited distinctive cellular interactions with respect to their mPEG grafting density. As a result, mPEG molecules demonstrated a minimal effect on the ZnS shell deposition and the Qdot fluorescence efficiency at a low mPEG density, whereas they showed pronounced effect on Qdot colloidal stability, protein binding affinity, cytotoxicity, and nonspecific binding at a higher mPEG grafting amount.",
author = "Mehriban Ulusoy and Rebecca Jonczyk and Walter, {Johanna Gabriela} and Sergej Springer and Antonina Lavrentieva and Frank Stahl and Mark Green and Thomas Scheper",
note = "Funding information: This work was carried out as an integral part of the BIOFABRICATION FOR NIFE Initiative (Lower Saxony Centre for Biomedical Engineering, Implant Research and Development in Hannover), which is financially supported by the Lower Saxony ministry of Science and Culture and the Volkswagen Foundation. Part of this work was also funded by the German Research Foundation (DFG) for the Cluster of Excellence REBIRTH (From Regenerative Biology to Reconstructive Therapy). R.J. acknowledges the Niedersachsische Krebsgesellschaft e.V. for financial support. We also thank Prof. Dr.-Ing. Birgit Glasmacher and Daniel Mueller (Institute of Multiphase Processes) for providing us access to the confocal microscope, Hamza Belhadj for his assistance in ATR-FTIR analysis, Paul Maschhoff (Department of Chemical Engineering, Northeastern University) for his support in editing the manuscript, and Marc Krey for his assistance in TG analysis.",
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AU - Ulusoy, Mehriban

AU - Jonczyk, Rebecca

AU - Walter, Johanna Gabriela

AU - Springer, Sergej

AU - Lavrentieva, Antonina

AU - Stahl, Frank

AU - Green, Mark

AU - Scheper, Thomas

N1 - Funding information: This work was carried out as an integral part of the BIOFABRICATION FOR NIFE Initiative (Lower Saxony Centre for Biomedical Engineering, Implant Research and Development in Hannover), which is financially supported by the Lower Saxony ministry of Science and Culture and the Volkswagen Foundation. Part of this work was also funded by the German Research Foundation (DFG) for the Cluster of Excellence REBIRTH (From Regenerative Biology to Reconstructive Therapy). R.J. acknowledges the Niedersachsische Krebsgesellschaft e.V. for financial support. We also thank Prof. Dr.-Ing. Birgit Glasmacher and Daniel Mueller (Institute of Multiphase Processes) for providing us access to the confocal microscope, Hamza Belhadj for his assistance in ATR-FTIR analysis, Paul Maschhoff (Department of Chemical Engineering, Northeastern University) for his support in editing the manuscript, and Marc Krey for his assistance in TG analysis.

PY - 2015/11/14

Y1 - 2015/11/14

N2 - Ligands used on the surface of colloidal nanoparticles (NPs) have a significant impact on physiochemical properties of NPs and their interaction in biological environments. In this study, we report a one-pot aqueous synthesis of 3-mercaptopropionic acid (MPA)-functionalized CdTe/CdS/ZnS quantum dots (Qdots) in the presence of thiol-terminated methoxy polyethylene glycol (mPEG) molecules as a surface coordinating ligand. The resulting mPEG-Qdots were characterized by using potential, FTIR, thermogravimetric (TG) analysis, and microscale thermophoresis (MST) studies. We investigated the effect of mPEG molecules and their grafting density on the Qdots photophysical properties, colloidal stability, protein binding affinity, and in vitro cellular toxicity. Moreover, cellular binding features of the resulting Qdots were examined by using three-dimensional (3D) tumor-like spheroids, and the results were discussed in detail. Promisingly, mPEG ligands were found to increase colloidal stability of Qdots, reduce adsorption of proteins to the Qdot surface, and mitigate Qdot-induced side effects to a great extent. Flow cytometry and confocal microscopy studies revealed that PEGylated Qdots exhibited distinctive cellular interactions with respect to their mPEG grafting density. As a result, mPEG molecules demonstrated a minimal effect on the ZnS shell deposition and the Qdot fluorescence efficiency at a low mPEG density, whereas they showed pronounced effect on Qdot colloidal stability, protein binding affinity, cytotoxicity, and nonspecific binding at a higher mPEG grafting amount.

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