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.
This study has been funded by the Agencia Estatal de Investigación (AEI) and Fondo Europeo de Desarrollo Regional (FEDER) (grant BIO2016-76063-R, AEI/FEDER, UE), AGAUR (2017SGR-229) and CIBER-BBN (project VENOM4CANCER) granted to AV, ISCIII (PI15/00272 co-founding FEDER) to EV. RD received an overseas predoctoral fellowship from Conacyt (Gobierno de México, 2016). LSG was supported by predoctoral fellowship from AGAUR (2018FI_B2_00051), NS was supported by a predoctoral fellowship from the Government of Navarra, and UU is supported by PERIS program from the health department of la Generalitat de Cataluña. AV received an ICREA ACADEMIA award.