Triggering Apoptosis Using Remotely Controlled Rotating Nanoparticles
Nanoparticle rotation via dynamic magnetic field shows potential for cancer therapy.
Researchers investigating the use of magnetic nanoparticles in the treatment of cancer have published a study suggesting their movement can be controlled remotely via a unique dynamic magnetic field (DMF) generator. The particles are thought to begin rotating when exposed to the magnetic field, and have the ability to tear up lysosomal walls, resulting in apoptosis.
The team covalently conjugated superparamagnetic iron oxide nanoparticles with antibodies targeting a lysosomal protein marker, and added them to rat insulinoma tumor and human pancreatic β-cell cultures. Following exposure to a DMF and confirmation that the particles had reached their targets, rotational nanoparticle movements were induced by applying the DMF again. The researchers hypothesized that the forces generated by the movement would injure lysosomal membrane structures, resulting in membrane permeabilization, extravasation of their contents into the cytoplasm and cell death.
The results of the study demonstrate how remotely controlling the conjugated iron oxide nanoparticles increased their cellular internalization, and that the particles successfully targeted the protein marker in both cell types, preferentially accumulating along the lysosomal membranes. A rapid decrease in size and number of lysosomes was observed following exposure to the DMF, and this was attributed to the rupturing of lysosomal membranes.
In the article, the authors state, “Our findings suggest that DMF treatment of lysosome-targeted nanoparticles offers a noninvasive tool to induce apoptosis remotely and could serve as an important platform technology for a wide range of biomedical applications.”
– Written by Kasumi Crews
Illustrated by Clare Dolan
Source: Zhang E, Kircher MF, Koch M, Eliasson L, Goldberg SN, Renström E. Dynamic magnetic fields remote-control apoptosis via nanoparticle rotation. ACS Nano 8(4), 3192–3201 (2014).
Novel Method to Assess Nanomaterial Toxicology
Volumetric centrifugation method could allow more reliable toxicological testing.
A team of researchers, led by scientists at Harvard School of Public Health (MA, USA), has developed a novel method to measure the density of engineered nanomaterials when they come into contact with living cells. The method, based on volumetric centrifugation, could have applications in toxicology, as well as potentially enabling researchers to develop new drug-delivery systems.
The novel method works by measuring the effective density of nanoagglomerates in suspension. The technique is based on the volume of the pellet obtained when nanomaterial suspensions are subjected to centrifugation, and is validated against gold standard analytical ultracentrifugation data. According to the team, the method is simple and cost effective, and could allow for accurate in vitro dosimetry.
The development of cost-effective toxicological screening methods for engineered nanomaterials is currently hampered by the lack of accurate in vitro dosimetry. It is hoped that this new technique will allow correct modeling of nanoparticle transport, and therefore more accurate dosimetry in cells. This, in turn, should allow the development of more reliable toxicological tests and further understanding of the interactions between nanomaterials and the biological environment in vivo. According to Joel Cohen, one of the lead authors of the study and PhD student at Harvard School of Public Health, “The volumetric centrifugation method will help nanobiologists and regulators to resolve conflicting in vitro cellular toxicity data that have been reported in the literature for various nanomaterials.”
– Written by Hannah Stanwix
Sources: DeLoid G, Cohen JM, Darrah T et al. Estimating the effective density of engineered nanomaterials for in vitro dosimetry. Nat. Commun. 5, 3514 (2014); Microscopic particles carry big concerns:http://news.harvard.edu/gazette/story/2014/03/microscopic-particles-carry-big-concerns
Light at The End of The Tunnel for Single-Molecule Imaging
Sub-10-nm upconverting particles could be a step forward for biological imaging.
Researchers from the Molecular Foundry at Lawrence Berkeley National Laboratory (CA, USA) have developed upconverting nanoparticles (UCNPs), which are capable of biological imaging at a single-molecule level.
Using advanced single-particle characterization techniques and computer modeling, the team discovered that surface effects are critical at diameters under 20 nm. They found that their previously developed UCNPs, comprising nanocrystals of sodium yttrium fluoride doped with trace amounts of ytterbium and erbium, were no longer bright enough for single-molecule imaging at diameters below 10 nm. However, by increasing the concentration of erbium to 20% and decreasing the concentration of ytterbium to 2% or less, the team succeeded in developing sub-10-nm particles that were bright enough for single-molecule imaging. This is a significant change from the previous concentrations, which were thought to optimal for brightness.
According to one of the lead authors of the study, Emory Chan, “People often assume that particles that are the brightest at low powers will also be the brightest at high powers, but we found our ultra-small UCNPs to be a classic tortoise-and-hare example. UCNPs heavily doped with erbium start slowly out of the gate, being incredibly dim at low powers, but by the time the laser intensity is cranked up to high power, they have passed the conventionally doped UCNPs that are the high-flyers at low powers.”
In future work, the team may investigate how to engineer particles consisting only of emitting elements, such as erbium, to give even brighter emissions.
– Written by Hannah Stanwix
Sources: Gargas DJ, Chan EM, Ostrowski AD et al. Engineering bright sub-10-nm upconverting nanocrystals for single-molecule imaging. Nat. Nanotechnol. 9(4), 300–305 (2014); Bright future for protein nanoprobes:http://newscenter.lbl.gov/news-releases/2014/03/17/bright-future-for-protein-nanoprobes
Light-Activated Antimicrobial Surface Is Also Effective in The Dark, Study Suggests
A new study, published recently in the journal Chemical Science, details how researchers from University College London (London, UK) have developed a new antibacterial material that may help reduce hospital infections.
Although hospitals try to reduce bacterial infections through strict cleaning policies, hospital-acquired infections are still a notable problem. Consequently, there is focus in research to find antibacterial coatings that will make surfaces less accommodating to bacteria.
One of the authors, Ivan Parkin explained: “There are certain dyes that are known to be harmful to bacteria when subjected to bright light. The light excites electrons in them, promoting the dye molecules to an excited triplet state and ultimately produces highly reactive oxygen radicals that damage bacteria cell walls. Our project tested new combinations of these dyes along with gold nanoparticles, and simplified ways of treating surfaces which could make the technology easier and cheaper to roll out.”
In this study, the researchers prepared bactericidal polymers by combining crystal violet, methylene blue and 2-nm gold nanoparticles into medical grade silicone. They observed that even under intense light levels and when cleaned with an alcohol-based wipe, the coating remained stable. Furthermore, when compared with other photobactericidal polymers against both Staphylococcus epidermidis and Escherichia coli, it exhibited the strongest currently reported photobactericidal activity. The most interesting finding was that it also demonstrated significant antimicrobial activity under dark conditions.
“Despite contaminating the surface with far more bacteria than you would ever see in a hospital setting, placed under a normal fluorescent light bulb, the entire sample was dead in 3–6 h, depending on the type of bacteria,” explained lead author, Sacha Noimark. “That was an excellent result, but the bigger surprise was the sample that we left in the dark. That sample also showed significant reductions in bacterial load, albeit over longer timescales of approximately 3–18 h. However, the precise mechanism by which this dark-kill works is not yet clear.”
– Written by Natasha Leeson
Sources: Noimark S, Allan E, Parkin IP. Light-activated antimicrobial surfaces with enhanced efficacy induced by a dark-activated mechanism. Chem. Sci. doi:10.1039/C3SC53186D (2014) (Epub ahead of print); UCL press release:www.ucl.ac.uk/news/news-articles/0314/240314-antimicrobial-surface