Recombinant ricin nanoparticles design for CXCR4+ cancer cell therapy

10^th World Congress on Medicinal Chemistry and Drug Design

June 14-15, 2018 | Barcelona, Spain

Raquel Diaz, Victor Pallares, Olivia Cano-Garrido, Naroa Serna, Laura Sanchez-Garcia, Aida Falgas, Mireia Pesarrodona, Ugutz Unzueta, Alejandro Sanchez-Chardi, Julieta M. Sanchez, Isolda Casanova, Esther V�¡zquez, Ramon Mangues and Antonio Villaverde

Universitat Aut�²noma de Barcelona, Spain
Biomedical Research Institute Sant Pau (IIB-Sant Pau) and Josep Carreras Research Institute Hospital de la Santa Creu i Sant Pau, Spain

Scientific Tracks Abstracts: Med chem (Los Angeles)

Abstract :

The potent ligand T22, that specifically binds the CXCR4+ receptor, overexpressed in some cancer cells, was engineered to be attached to the N-terminus of the mutated A chain of the plant toxin ricin fused to a 6xHis tag in the C-terminus. The soluble recombinant protein T22mRTAH6 spontaneously self-assembled as protein-only regular nanoparticles of about 12nm in size, capable of CXCR4 dependent cellular internalization and effective cytotoxic effect in vitro. Meanwhile, the insoluble version of the protein presented moderate free-protein release inducing to a partial cytotoxic effect in the cells. The T22mRTAH6 nanostructured construct was also tried in mouse models of acute myeloid leukemia, where it proved to reduce dramatically the disease affectation of clinically relevant organs. The functionalized protein nanoparticles are then proposed as suitable prototypes for antitumor carcinogenic therapies based on self-mediated intracellular drug delivery

Biography :

Raquel Díaz is studying her PhD program at Univerity Autonomous of Barcelona .

E-mail: raquel.diazoca@gmail.com