Atonomous University of Barcelona, Spain
Title: Therapeutic protein-only nanoparticles as targeted antitumoral drugs
Biography: Laura Sánchez-García
Nowadays, conventional cancer treatments present high systemic toxicity, leading to side effects on healthy tissues. For that reason, it is of great relevance to develop targeted drugs that can increase the local drug concentration, minimize toxic effects on off-target tissues and reduce the dose administered. Moreover, loading capacity and drug leakage from vehicles during circulation in blood is a major concern when developing nanoparticle-based cell-targeted cytotoxics. To circumvent this potential issue it would be convenient the engineering of drugs as self-delivered nanoscale entities, devoid of any heterologous carriers. In this context, we have engineered potent protein toxins, using the active fragments of the diphtheria toxin and the Pseudomonas aeruginosa exotoxin, as self-assembling, self-delivered therapeutic materials targeted to CXCR4+ cancer stem cells. CXCR4 receptor is overexpressed in a variety of human cancers and plays a critical role in metastatic process. For this reason, we have fused T22 to the toxic domains (T22-TOXIN-H6), as it is a CXCR4 ligand able to bind specifically and internalize into the target cells.
The systemic administration of both nanostructured drugs in a colorectal cancer xenograft mouse model promotes efficient and specific local destruction of target tumor tissues and a significant reduction of the tumor volume. This observation strongly supports the concept of intrinsically functional protein nanoparticles, which having a dual role as drug and carrier, are designed to be administered without the assistance of heterologous vehicles. The promising results obtained have allowed the development of a new patent (EP17169722) that has been licensed to NANOLIGENT SL.