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A Quantum Dot-Protein Bioconjugate That Provides for Extracellular Control of Intracellular Drug Release
- Source :
- Bioconjugate Chemistry. 29:2455-2467
- Publication Year :
- 2018
- Publisher :
- American Chemical Society (ACS), 2018.
-
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 the cytosol until the addition of maltose to the extracellular medium, which underwent facilitated uptake into the cell. Live cell FRET-based confocal microscopy imaging captured the kinetics of realtime release of the βCD ligand as a function of extracellular maltose concentration. Our results demonstrate the utility of the self-assembled QD-MBP-βCD system to facilitate intracellular drug release that is triggered extracellularly through the simple addition of a well-tolerated nutrient and is not dependent on the use of light, magnetic field, ultrasound, or other traditional methods of stimulated drug release. We expect this extracellularly triggered drug release modality to be useful for the in vitro characterization of new drug candidates intended for systemic delivery/actuation and potentially for on-demand drug release in vivo.
- Subjects :
- Biomedical Engineering
Pharmaceutical Science
Bioengineering
02 engineering and technology
010402 general chemistry
Binding, Competitive
01 natural sciences
Maltose-Binding Proteins
Maltose-binding protein
Drug Delivery Systems
Chlorocebus aethiops
Quantum Dots
Extracellular
Animals
Humans
Maltose
Pharmacology
Binding Sites
Bioconjugation
biology
Chemistry
beta-Cyclodextrins
Organic Chemistry
021001 nanoscience & nanotechnology
Ligand (biochemistry)
0104 chemical sciences
Drug Liberation
Förster resonance energy transfer
COS Cells
Drug delivery
Biophysics
biology.protein
0210 nano-technology
Intracellular
Biotechnology
Conjugate
Subjects
Details
- ISSN :
- 15204812 and 10431802
- Volume :
- 29
- Database :
- OpenAIRE
- Journal :
- Bioconjugate Chemistry
- Accession number :
- edsair.doi.dedup.....a88ed363af5fd053b9817dc59e480bd4