Engineering protein toxins as self-assembling, self-delivered antitumoral drugs.

LAURA SÁNCHEZ-GARCIA; VICTOR PALLARÈS ; RAQUEL DÍAZ; PATRICIA ÁLAMO, ; NAROA SERNA; Mª VIRTUDES CÉSPEDES, ; OLIVIA CANO-GARRIDO; AÏDA FALGÀ, ; RITA SALA,; MIREIA PESARRODONA; UGUTZ UNZUETA ,; ALEJANDRO SÁNCHEZ-CHARDI, MÒNICA ROLDAN; J. M. SANCHEZ; ISOLDA CASANOVA, ; ESTHER VÁZQUEZ ; RAMÓN MANGUESANTONIO VILLAVERDE; ANTONIO VILLAVERDE

París

Encuentro; 25th Meeting of the French Society of Toxinology (SFET); 2018

Cell targeted drug delivery is especially appealing for the systemic administration of cytotoxic drugs (such as in oncology), to reduce side toxicity and to increase the therapeutic index. Nanoscale drug vehicles composed of different materials are under continuous development. However, because of the potential harmfulness and lack of therapeutic activity of most nanomaterials, the convenience of generating vehicle-free, self-assembled and cell-targeted drugs has been recently stressed (Shen, et al., 2017). For that, proteins are excellent biomaterials, since they can be engineered to recruit the functions necessary for self-assembling as nanosized multifunctional agents (Vazquez, et al., 2016). In this context, we have recently engineered the Diphtheria toxin, the Pseudomonas aeruginosa toxin (Sanchez-Garcia, et al., 2018) and the plant toxin ricin (Diaz, et al., 2018), to organize as biologically active nanoparticles that bind, penetrate and selectively kill CXCR4+ metastatic cancer stem cells. When tested in animal models of human neoplasias, such as colorectal cancer and acute myeloid leukemia, a dramatic reduction of metastatic foci have been observed. This is fully supporting the concept of toxins as potent antimetastatic drugs but also the potential of toxin-based self-assembling, self-delivered and self-targeted protein drugs for precision medicine (Serna, et al., 2018).