Antitumoral nanoparticles with multiple activities, a close reality

ERIC VOLTA DURAN; NAROA SERNA; LAURA SÁNCHEZ-GARCIA; JULIETA M. SANCHEZ; HECTOR LOPEZ LAGUNA; ERITJA, RAMON; RAMON MANGUES; ESTHER VÁZQUEZ; ANTONIO VILLAVERDE; UGUTZ UNZUETA ,

Santander

Conferencia; 3rd International Conference on Nanomaterials Applied to Life Sciences 2022; 2022

Universidad de Cantabria

Targeted therapies represent a promising alternative to current chemotherapies for cancer treatment. Most of them are based on nanocarriers that selectively deliver conventional chemical drugs merely to their target cells, avoiding potential side-effects. An alternative emerging concept involves the use of self-assembled nanodrugs based on proteins with antitumoral activities, such as tumor-targeted toxins, venoms or proapoptotic factors. Our research is focused on targeting CXCR4, a surface receptor overexpressed in metastatic stem cells of 23 human neoplasias and whose overexpression is correlated with bad prognosis. For that purpose, we use the potent peptidic CXCR4-ligand T22. We have previously developed targeted protein nanoparticles carrying chemical drugsand targeted protein nanoparticles based on bacterial toxins, both promoting significant antitumoral activities in vitro and in mice models of a wide range of CXCR4+ cancers. Recently, we have explored the possibility of combining both strategies to generate intrinsically toxic nanoparticles loaded with conventional chemotherapeutics in a single pharmacological entity [1]. This way, we seek to potentiate their antitumoral effect and face the appearance of resistances in the tumor. In this initial step, the concept proposed has been demonstrated as fully feasible, as stable nanoparticles that contain both the toxin and the loaded chemotherapeutics were generated. Although these novel nanomaterials do not improve toxin activities in vitro, this research has been crucial to identify the main bottleneck of the technology, that is achieving a precise control of the drug-binding site. This novel platform, that recruits in a single pharmacological entity different therapeutic actions may open a broad investigation field in the design of antitumoral drugs.