A Quantum Dot-Protein Bioconjugate That Provides for Extracellular Control of Intracellular Drug Release

Bioconjugate Chemistry
Lauren D FieldJames B Delehanty

Abstract

The ability to control the intracellular release of drug cargos from nanobioconjugate delivery scaffolds is critical for the successful implementation of nanoparticle (NP)-mediated drug delivery. This is particularly true for hard NP carriers such as semiconductor quantum dots (QDs) and gold NPs. Here, we report the development of a QD-based multicomponent drug release system that, when delivered to the cytosol of mammalian cells, is triggered to release its drug cargo by the simple addition of a competitive ligand to the extracellular medium. The ensemble construct consists of the central QD scaffold that is decorated with a fixed number of maltose binding proteins (MBPs). The MBP binding site is loaded with dye or drug conjugates of the maltose analogue beta-cyclodextrin (βCD) to yield a QD-MBP-βCD ensemble conjugate. The fidelity of conjugate assembly is monitored by Förster resonance energy transfer (FRET) from the QD donor to the dye/drug acceptor. Microplate-based FRET assays demonstrated that the βCD conjugate was released from the MBP binding pocket by maltose addition with an affinity that matched native MBP-maltose binding interactions. In COS-1 cells, the microinjected assembled conjugates remained stably intact in t...Continue Reading

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Citations

Apr 29, 2020·Micromachines·Alana Torres VidalHieu Bui
Sep 29, 2020·Chemphyschem : a European Journal of Chemical Physics and Physical Chemistry·Sucheta BanerjeeAnindya Datta
Jan 6, 2021·Topics in Current Chemistry·Sueden O SouzaGoreti Pereira
Jul 21, 2021·Chemical Reviews·W Russ AlgarHyungki Kim

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