Engineering a recombinant chlorotoxin as celltargeted cytotoxic nanoparticles

RAQUEL DÍAZ; LAURA SÁNCHEZ-GARCIA; NAROA SERNA; ALEJANDRO SÁNCHEZ-CHARDI; OLIVIA CANO-GARRIDO; JULIETA M. SÁNCHEZ; UGUTZ UNZUETA ,; ESTHER VÁZQUEZ; ANTONIO VILLAVERDE

Science China Materials

Science China Press and Springer

Lugar: Pekín; Año: 2019 vol. 1

2095-8226

The controlled oligomerization of functional proteins as nanoscale materials offers the possibility to design and produce, in a recombinant way, 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 alsoexhibit a mild but still significant cytotoxic activities 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.