A new system for delivering quantum dots to living cells
Maria Kostyukova, Nanonews NetworkThe study of the processes occurring in living cells requires the development of new research methods in which the cell does not undergo drastic and destructive changes.
Scientists from the University of Toronto have presented a new non-invasive strategy for creating multifunctional nanosystems for studying intracellular processes in living cells.
Widely used in modern cellular research, quantum dot class nanoparticles (QDs) serve as fluorescent probes and capsules for targeted drug delivery. Due to the high chemical stability, the possibility of varying the fluorescent properties and conjugation of biologically active molecules with the QDs surface, these nanoparticles can be used by scientists to study processes inside cells. However, the use of microscopy in the visualization of cellular processes is complicated by the accumulation of QDs in endosomes and on cell membrane receptors. This is a big disadvantage in the tasks of releasing a large amount of QDs into the cytoplasm and causes serious damage to the cell membrane and hinders the normal functioning of cellular organelles involved in protein transport.
Scientists at the University of Toronto, led by Professor Warren Chan, have developed a new strategy for moving quantum dots inside the cell, which is not accompanied by damage to the membrane and the accumulation of nanoparticles in it.
The nanoparticles were encapsulated in a biodegradable hydrogel and modified with antibodies specifically binding to cell membrane receptors. The resulting nanocomposite structure consisting of QDs penetrates into cells without destroying the membrane, and then hydrolyzes in the cytoplasm, releasing individual QDs nanoparticles.
Earlier attempts by scientists to carry out the transport of peptides into the cell using nanoparticles were unsuccessful due to the natural membrane mechanisms of the cell, limiting the ingress of foreign objects into it. Other methods, such as microinjections and electroporation, are not sufficiently productive and severely damage cells.
The only method that allows high–performance and without destruction of the membrane to transport substances into the cell is to use the phagocytic feature of the membrane, that is, the specific binding of antibodies covering the nanoparticle to the membrane receptors and subsequent endocytosis of the particle. Once in the cell, the nanoparticle is hydrolyzed, releasing the delivered QDs into the cytoplasm. Thus, a high concentration of nanoparticles, drugs or bioconjugate is achieved in the immediate vicinity of target proteins in the cell.
Mechanism of release and intracellular directed action of quantum nanodots.
The capture and endocytosis of a biodegradable nanoparticle coated with antibodies to cell membrane receptors is schematically depicted, followed by its hydrolysis in the cell cytoplasm and the release of QDs nanoparticles encapsulated in it to affect intracellular structures
"The biocompatibility of the nanoparticle delivery system developed by us significantly expands the horizons of possible applications of QDs for the study of intracellular structures and fundamental processes directly in a living cell," says Professor Chan. "We observe a significant improvement in the biocompatibility of our nanostructures compared to simple QDs and therefore expect minimal cytotoxicity."
This approach allows the simultaneous introduction into the cell of nanoparticles with several cellular markers encapsulated in them, having different fluorescent characteristics.
The results of the work were published in the journal Nano Letters (Biodegradable Quantum Dot Nanocomposites Enable Live Cell Labeling and Imaging of Cytoplasmic Targets).
Further research by scientists will be devoted to a detailed study of the behavior of nanocomposites based on quantum dots inside the cell, since only this knowledge can provide a complete understanding of the nuances and capabilities of the new technology.