Carbon Nanotube Sensors Could Aid Drug Manufacturing
Uniform nanoarrays have been developed that are capable of detecting flaws in engineered antibody-based drugs.
Researchers at Michigan Institute of Technology (MI, USA) have created a nanosensor array capable of characterizing the variations in the binding strengths of antibody drugs, a tool that could be useful in investigating the efficacy of future drug formulations.
The team also demonstrated the ability of the nanosensor to determine which cells in a population of genetically engineered, drug-producing cells are the most productive or desirable. According to Michael Strano, MIT Professor of Chemical Engineering and research group leader, “This could help pharmaceutical companies figure out why certain formulations work better than others, and may help improve their effectiveness.”
Previously, the group had demonstrated that carbon nanotube-based sensors are capable of specific target recognition by binding to proteins and producing a detectable, fluorescent signal change. Through the exploitation of large arrays of such sensors, Strano and his team discovered that uniform arrays are capable of measuring the distribution of binding strength in antibodies and other complex proteins.
When antibodies bind to cancer cell proteins the body‘s immune system is activated to attack the tumor. The current manufacturing method for antibody drugs, which relies on engineered cells, is not capable of generating consistent and uniformly binding batches. “You could use the technology to reject batches, but ideally you would want to use it in your upstream process development to generate a more consistent product”, said Nigel Ruel (Michigan Institute of Technology), lead author of the study.
The sensors were also able to measure weak binding interactions, as well as map the production of a molecule of interest. According to Ramon Wahl, author of the paper and a principal scientist at Novartis (Basel, Switzerland), “Carbon nanotubes coupled to protein-binding entities are interesting for several areas of biomanufacturing as they offer great potential for online monitoring of product levels and quality. Our collaboration has shown that carbon nanotube-based fluorescent sensors are applicable for such purposes, and I am eager to follow the maturation of this technology.” The team plan to test a briefcase-sized prototype of their sensor with Novartis and the National Science Foundation (VA, USA).
– Written by Phoebe Heseltine
Source: Reuel N, Grassbaugh B, Kruss S et al. Emergent properties of nanosensor arrays: applications for monitoring IgG affinity distributions, weakly affined hypermannosylation, and colony selection for biomanufacturing. ACS Nano doi:10.1021/nn403215e (2013) (Epub ahead of print).
Temperature-Sensitive Polymers Capable of Regulating Self-Assembly Improved Drug Delivery
‘Smart’ self-assembly of polymers could lead to highly controlled drug delivery.
Chemists at Syracuse University College of Arts and Sciences (NY, USA) have designed a temperature-sensitive polymer capable of regulating DNA interactions in both a DNA-mediated assembly system and a DNA-encoded drug-delivery system.
Associate Professor, Mathew Maye (Syracuse University College of Arts and Sciences), and his team synthesized a ‘smart’ polymer that is temperature reactive and assembled via gold nanoparticles. Through this approach, the nanoparticle possesses short segments of single-stranded DNA. “This multipurpose functionality and added smart component are indicative of where nanoscience is going. We want nanomaterials to perform many tasks at once and we want to be able to turn their actions on and off remotely,” said Maye.
During self-assembly, the chemical component adhered to the nanoparticle interface drives the reaction. As a result, particles come together to form a small-molecule cluster due to the high temperatures. The nanocarrier invented at Syracuse University has a sixfold increase in toxicity compared to those used in previous studies.
According to Maye, “Being able to control nanoparticle assembly with temperature allows us to fine tune their reactions and form more predictable structures. It also gives us a more improved system in which to scale assembly”. He continued, “When combined with thermosensitive polymers such as the ones in our system, they could become very lucrative.”
– Written by Phoebe Heseltine
Source: Hamner K, Alexander C, Coopersmith K et al.Using temperature-sensitive smart polymers to regulate DNA-mediated nanoassembly and encoded nanocarrier drug release. ACS Nano 7(8), 7011–7020 (2013).
DNA Nanobots Target Cells for Drug Therapy or Destruction
Researchers design automated DNA nanobot capable of identifying multiple targets.
Researchers at Columbia University Medical Center (NY, USA) have created molecular robots capable of seeking a specific set of human blood cells and attaching a fluorescent tag to their surface. In collaboration with the Hospital for Special Surgery (NY, USA), the team constructed three different components for automation. Each component consisted of double-stranded DNA attached to an antibody that was specific to a surface protein. With the components combined, the antibody parts of the robot became bound to their respective proteins.
According to Milan Stojanovic, Associate Professor of Medicine and Biomedical Engineering at Columbia University, “This opens up the possibility of using such molecules to target, treat or kill specific cells without affecting similar healthy cells. In our experiment, we tagged the cells with a fluorescent marker, but we could replace that with a drug or toxin to kill the cell.”
The DNA nanobots are novel in that they are able to distinguish cell populations that do not share distinctive features. Previously, it has been difficult to design drugs without side effects for this reason, but when cells are targeted to identify a collection of features, they can be identified based on multiple proteins.
“We have demonstrated our concept with blood cells because their surface proteins are well known, but in principle our molecules could be deployed anywhere in the body. In addition, the system can be expanded to identify four, five or even more surface proteins,” said Stojanovic. The team will continue the development of the DNA nanobots with tests in living mouse models.
– Written by Phoebe Heseltine
Source: Rudchenko M, Taylor S, Pallavi P et al. Autonomous molecular cascades for evaluation of cell surfaces. Nat. Nanotechnol. doi:10.1038/nnano.2013.142 (2013) (Epub ahead of print).
Mitochondria-Targeted Nanoparticles May Be An Effective Immunotherapeutic in Combating Cancer
Researchers at the University of Georgia (GA, USA) have reported on the therapeutic potential of laser light-activated, mitochondria-targeting nanoparticles (NPs) in activating dendritic cells to effectively provoke an immune attack on cancer cells.
The study describes the treatment of breast cancer cells with NPs based on a biodegradable polymer and a zinc phthalocyanine photosensitizer. The investigation, which was led by Shanta Dhar, an Assistant Professor at the University of Georgia, found that, upon light stimulation, the NPs activate tumor antigens, eliciting the production of high levels of IFN-γ from dendritic cells. “These high levels alert the rest of the immune system to a foreign presence and signalling it to attack the cancer cells” explained Dhar.
According to the report, these findings may potentially open up the possibility of using mitochondria-targeted, NP-treated, light-activated cancer cell supernatants as possible vaccines for the prevention and treatment of cancer.
– Written by Hannah Coaker
Source: Marrache S, Tundup S, Harn DA, Dhar S. Ex vivoprogramming of dendritic cells by mitochondria-targeted nanoparticles to produce interferon-g for cancer immunotherapy. ACS Nano doi:10.1021/nn403158n (2013) (Epub ahead of print).