Novel nanoparticle releases therapy via DNA sequence trigger
Medical science has produced a wide range of nanoparticles for delivery of cytotoxic drugs to treat cancer, but have experienced a lot of frustration in coming up with the ideal trigger for release of that therapy. Researchers in Germany and Sweden may have answered that question quite capably with a mucin-based nanoparticle that is designed to react to a specific DNA sequence, one that is specific to the cancer cell. This approach requires the collection of porcine mucin, which is paired with a carboxy-modified ATTO dye to enable fluorescence labeling. The researchers determined that 13 CRISPR-edited DNA (crDNA) molecules can be attached to each mucin molecule, so long as the crDNA conjugation takes place prior to coating of the mucin with poly(L-lysine). Following this, the trigger DNA is attached to the crDNA-crosslinked mucin nanoparticles, and the resulting construct is fairly resistant to enzymatic attack. Electrostatic interactions seem to play a role in fixation of the therapeutic drug to this nanoparticle delivery system, and the scientists chose doxorubicin for an in vitro evaluation of this arrangement. The result was a demonstration of drug release “into the cytosol with high efficiency,” the authors said, adding that a cancer that overexpresses a specific microRNA sequence can be targeted in this fashion. The authors said this approach can aid in the design of site-specific treatments for diseases in which “an overexpression of signature oligonucleotide sequences has been identified.” These findings are explained in more detail in the Aug. 7, 2020, online issue of ACS Nano.
In AML, collapse prevents relapse
Researchers at Harvard University have discovered that by inducing what they termed a “timed metabolic collapse,” they were able to overcome resistance to chemotherapy in mouse models and patient-derived xenografts of acute myeloid leukemia (AML). Chemotherapy can often induce complete remissions in AML patients, but those are often followed by relapse initiated by rare cells that survive chemotherapy. The researchers hypothesized that the cells that were able to survive chemotherapy did so by rewiring their metabolism, and they used unbiased metabolomic profiling of cells that survived chemotherapy to identify distinct forms of glutamine metabolism and pyrimidine synthesis in post-chemotherapy, pre-relapse tumor cells. By disrupting those metabolic adaptations, the team was able to select against residual cells and improve survival in preclinical models. The authors “propose that timed cell-intrinsic or niche-focused metabolic disruption can exploit a transient vulnerability and induce metabolic collapse in cancer cells to overcome chemoresistance.” They published their proposal, and the data supporting it, in the Aug. 6, 2020, online issue of Cell Metabolism.
The next great nano-thing: nanopaper
Many years have passed since the legendary Buckyball made headlines, but research into nano-things continues despite the nearly four decades that have passed since the first creation of a Buckminsterfullerene. Researchers in Canada have taken a decidedly flatter approach with nanopaper-based devices they say can perform superbly as microfluidics for a number of applications. Conventional cellulose-based paper fabrications have faltered because of impeded flow velocity, but these researchers san nanopaper-based versions, such as nanopaper-based analytical devices (nanoPADs) and nanofibrillated adherent cell-culture platforms (nanoFACES) provide pump-free microfluidics that avoid the need for surface chemical functionalization. The use of nanopaper to fabricate these nanoPADs and nanoFACES allows the integration of optical sensing and imaging technologies, making them ideal for detection of specific cell types as well as cell biology studies. This research is described in the July 28, 2020, issue of Lab on a Chip.