RGDfK-functionalized ultrasmall silica nanoparticles as treatment of glioblastoma under normoxic and hypoxic conditions

Abstract

According to the World Health Organization, one of the most deadly diseases in the world is cancer. With over 100 types of cancer detected, this disease is constantly changing, making it difficult to choose of treatment. Some types of cancer are silent, and when diagnosed late they are in malignant progression and metastasis. Tumors in the advanced stage are highly vascularized, but unbalanced. In this case, the cells rapidly proliferate performing anaerobic respiration. As a consequence, a high concentration of lactic acid appears, leading to a decrease in the pH of the medium, known as tumor hypoxia. Based on this, much research has been done on how to reverse this tumor cell-modified metabolic process. In this context, drugs that block lactate output as a signaling agent and alternative therapies that do not cause side effects, such as NO therapy, are being recently explored. In addition, drug-associated vectorized nanoparticles are in what we know about the state of the art of nanomedicine, especially in overcoming the blood brain barrier when related to glioblastoma. In this context, this BEPE project aims to therapeutically apply ultra-small silica nanoparticles to glioma cancer cells under normoxia and hypoxia conditions. Si NPs will carry CHCA and N- [4-nitro-3- (trifluoromethyl)phenyl] propane-1,3-diamine (NOP) as the release blocker for extracellular lactate and photodon or NO, respectively; with further functionalization with cyclic peptide RGDfK for selective delivery. (AU)