In silico, in vivo, in vitro approach opens doors for nanoparticle-based drug discovery

(Nanowerk News) The medical community is armed with new insights and new options for drug design and discovery to treat fatal diseases such as pancreatic cancer. Using in silico computational tools to complement the results of in vivo and in vitro experiments, researchers revealed an atomic-level understanding of the mechanism by which nanoparticles inhibit the growth and metastasis of pancreatic tumors ("Molecular mechanism of pancreatic tumor metastasis inhibition by [email protected]82(OH)22 and its implication for de novo design of nanomedicine").
Gd@C82(OH)22 is a spherical cage of carbon atoms
[email protected]82(OH)22 is a spherical cage of carbon atoms (blue) with active hydroxyl groups dangling on the outside (red and white) and an atom of gadolinium trapped on the inside (purple). Originally developed for medical imaging, these nanoparticles now show promise for treating pancreatic cancer. (Image: IBM)
The nanoparticle type at the center of this study is gadolinium metallofullerenol, or [email protected]82(OH)22, which was originally developed for medical imaging applications such as MRI. Also central to the study are two popular anticancer therapy targets, MMP-2 and MMP-9. These MMPs, or matrix metalloproteinases, are key to the survival of cancer cells because they help bring a supply of blood vessels, and therefore oxygen and nutrients, to tumor sites.
Experiments showed that nanoparticle therapy blocked pancreatic tumor growth in mice and, at the cellular level, suppressed the expression and reduced the activities of MMP-2 and MMP-9. Computational simulations revealed that the nanoparticlesí action on MMP-9 is indirect such that they bind to the protein far from its active site. This is in distinct contrast to traditional molecular medicines that typically target the MMP active metal-binding site, directly blocking it or damaging the proteinís structure.
The nanoparticles were so effective that the teamís data suggest they may be a better pancreatic cancer therapy option than traditional medicines. Moreover, the teamís integrated use of computational theory to complement experimental data offers a new understanding, with unprecedented mechanistic detail, of the interactions between nanoparticles and biological molecules, bringing us into uncharted and promising new territory for drug design and discovery.
Source: Pacific Northwest National Laboratory
Subscribe to a free copy of one of our daily
Nanowerk Newsletter Email Digests
with a compilation of all of the day's news.
These articles might interest you as well: