Carbon Nanodots for Intracellular Imaging and Drug Delivery Tracking

By Benedette Cuffari, M.Sc.Feb 15 2017

Nanoparticles are microscopic particles with at least one dimension measuring less than 100 nm. Due to this size, these particle exhibit characteristics that differ greatly from the bulk material of the same substance. For example, gold nanoparticles appear deep red to black in a solution and copper nanoparticles smaller than 50 nanometers (nm) are extremely hard, lacking the typical ductility of bulk copper.

This change in the physical properties of the material is believed to be attributed to the higher percentage of atoms present at the surface relative to the total number of atoms in the particle¹. As a result of these varying characteristics, nanoparticle research is one of the most widely studied areas, with applications present in the fields of biomedical, optical and electronic fields.

Carbon nanoparticles (CNP), also known as nanodots or nanopowder, are black, spherical particles, typically of a diameter within the range of 10-45 nm, with a highly specific surface area high surface area ranging from 30 – 50 m²/g². Some of the applications of CNPs are actively used today in the fields of cancer treatment and osteopathic medicine. For example, CNPs called nanodiamonds have been used to tag protein molecules in order to increase bone growth around dental and joint implants³. Similarly, CNPs, in combination with gold nanoparticles, have been used to heat and destroy tumors in cancer therapies by manipulating radio waves in lymphomas and even metastasized cancer².

Some of the most recent applications of CNPs are shown in its use in multiscale imaging, in which their ability to resist photobleaching, while remaining of low toxicity at a minimized cost for large-scale production needs, make its addition of particular interest to researchers. In fact, researchers in the Department of Bioengineering at the University of Illinois have recently shown that photo luminescent CNPs can display a reversal of their optical properties in cancer cells. This reversible switching of photoluminescence (PL) is possible by counterionic caging and decaging of carbon nanoparticles at the nanoscale⁴.

Highly luminescent and negatively-charged CNPs were prepared hydrothermally from Agave nectar, which is a natural carbohydrate source of the photoluminescent CNPs. The surfaces of these “bare” CNPs were then coated with a variety of cationic, or positively charged, macromolecules, such as branched polyethylenimine (PEI), polypeptidic poly L-lysine (polyLys) and dendritic poly amidoamine (PAMAM+), in order to create ‘caged’-CNPs⁴. These caged CNPs could only regain their luminescence by “decaging,” a process that is dependent upon its interaction with anionic, or negatively charged, surfactant molecules. Although anionic sodium dodecyl sulfate (SDS) and nonionic polyethylene glycolcety- lether (PEGCE) were used for the decaging processes, aggregates of about 1100 nm were formed with SDS however, no such events were observed with non-ionic surfactant PEGCE⁴.

In order to confirm the ability of both caged and decaged CNPs to interact with both the anionic and cationic agents, gel electrophoresis and in vitro studies were performed. Gel electrophoresis techniques studied the ability of CNP, PEI and caged-CNP (CNP-PEI) to interact with or without the presence of SDS, in which DNA was also used as a secondary negatively charged molecule to compete against the positively charged molecules⁴. It was found that PEI-DNA was capable of interrupting the attraction by SDS, leading to a release of DNA, which confirms the ability of PEI caging and decaging on CNPs. Furthermore, it was found that caged-CNPs require the presence of an ionic surfactant in order to free DNA.

In vitro studies involved the addition of bare CNPs and CNP-PEIs to breast cancer MCF-7 cells, in which plates were then incubated for 24 hours, and then fixed with their given CNPs at either 1 or 2.5 hour time points post-incubation⁴. Here, the addition of an endosomal tracking die confirmed the presence of CNPs within the intracellular space, as well as within the endosomal membranes, which were far more luminescent at the longer time point of 2.5 hours. This increased behavior has been speculated to be a result of the CNP-surface bound cationic branched macromolecular amines to form complexes with the anionic lipids that are present within the endosomal membranes, resulting in a similar decaging of CNP-PEIs that was found in the previous gel electrophoresis studies⁴. By understanding the ability to reversibly switch the PL potential of CNPs through these varying “caging” and “decaging” processes at the nanoscale, researchers are hopeful that future biological processes can be studied in a similar manner.

References:

1. "Luminescence Switchable Carbon Nanodots Follow Intracellular Trafficking and Drug Delivery." ScienceDaily. ScienceDaily, 13 Feb. 2017. Web. https://www.sciencedaily.com/terms/nanoparticle.htm.
2. "Carbon Nanoparticles." American Elements. 18 Aug. 2016. Web. https://www.americanelements.com/carbon-nanoparticles-7440-44-0.
3. "Nanoparticle Applications and Uses ." Understanding Nano. Web. http://www.understandingnano.com/nanoparticles.html.
4. Santosh K. Misra, Indrajit Srivastava, Indu Tripathi, Enrique Daza, Fatemeh Ostadhossein, Dipanjan Pan. “Macromolecularly “Caged” Carbon Nanoparticles for Intracellular Trafficking via Switchable Photoluminescence.” Journal of the American Chemical Society, 2017; 139 (5): 1746.
5. Image Credit: shutterstock.com/giroscience

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