Dr. A. Villaverde: Engineering a recombinant chlorotoxin as cell-targeted cytotoxic

Abstract

The controlled oligomerization of functional proteins at the nanoscale offers the possibility to design and produce, by recombinant DNA technologies, improved materials and drugs. A recombinant version of the scorpion toxin chlorotoxin (CTX), which has attracted interest due to its ability to preferentially bind cancer cells, has been engineered to self-assemble as regular 12 nm-nanoparticles that penetrate cultured cells with the same receptor-specificity than the natural toxin. These materials, that appear as promising, biocompatible and biodegradable drug carriers for cell-targeted therapy of glioma also exhibit a mild but still significant cytotoxic activity associated to the recombinant toxin, that simultaneously acts as both driver and therapeutic agent. In addition, the manipulation of the CTX-flanking regions shows a potent impact on the performance of the nanoparticles, supporting a high functional versatility of CTX-based constructs, regulatable by conventional genetic engineering.