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Quantum dot-enabled membrane-tethering and enhanced photoactivation of chlorin-e6

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Abstract

Photodynamic therapy (PDT) has emerged as an attractive therapeutic modality for the targeted destruction of abnormal cells as it involves the specific generation of reactive oxygen species (ROS) in tissue only in the combined presence of a photosensitizer (PS), incident excitation light, and molecular oxygen. A variety of effective PS molecules have been developed but they are often limited by poor water solubility or a lack of cell-type specificity. We have developed a quantum dot-chlorin e6 (QD-Ce6) nanobioconjugate system where the QD (5 nm diameter) serves simultaneously as a hydrophilic scaffold and an efficient Förster resonance energy transfer (FRET) donor to multiple Ce6 PS acceptors arrayed around the central QD. Decoration of the conjugate with a membrane-tethering peptide stably localizes the ensemble conjugate system on the exofacial leaflet of the plasma membrane of mammalian cells. Excitation of Ce6 in a FRET configuration results in membrane-localized ROS generation resulting in lipid peroxidation, increased membrane permeability, and inhibition of cellular proliferation. We present and discuss our results in the context of the further evolution of QD-based PDT systems.

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Acknowledgements

A.S. was a Ph.D. candidate in the Fischell Department of Bioengineering, University of Maryland College Park, MD.

The authors acknowledge the NRL Base Funding Program and the NRL Institute for Nanoscience for financial support.

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Correspondence to James B. Delehanty.

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Sangtani, A., Nag, O.K., Oh, E. et al. Quantum dot-enabled membrane-tethering and enhanced photoactivation of chlorin-e6. J Nanopart Res 23, 159 (2021). https://doi.org/10.1007/s11051-021-05297-z

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