Algorithm for Designing Nanoscale Supramolecular Therapeutics with Increased Anticancer Efficacy

ACS Nano. 2016 Sep 27;10(9):8154-68. doi: 10.1021/acsnano.6b00241. Epub 2016 Jul 29.


In the chemical world, evolution is mirrored in the origin of nanoscale supramolecular structures from molecular subunits. The complexity of function acquired in a supramolecular system over a molecular subunit can be harnessed in the treatment of cancer. However, the design of supramolecular nanostructures is hindered by a limited atomistic level understanding of interactions between building blocks. Here, we report the development of a computational algorithm, which we term Volvox after the first multicellular organism, that sequentially integrates quantum mechanical energy-state- and force-field-based models with large-scale all-atomistic explicit water molecular dynamics simulations to design stable nanoscale lipidic supramolecular structures. In one example, we demonstrate that Volvox enables the design of a nanoscale taxane supramolecular therapeutic. In another example, we demonstrate that Volvox can be extended to optimizing the ratio of excipients to form a stable nanoscale supramolecular therapeutic. The nanoscale taxane supramolecular therapeutic exerts greater antitumor efficacy than a clinically used taxane in vivo. Volvox can emerge as a powerful tool in the design of nanoscale supramolecular therapeutics for effective treatment of cancer.

Keywords: cancer; drug delivery; molecular dynamics simulations; supramolecular nanoparticles; taxanes.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Algorithms*
  • Molecular Dynamics Simulation
  • Nanoparticles*
  • Nanostructures
  • Neoplasms / therapy*