Nanosystems containing proton "sponge"/gold nanoparticles for tumor hypoxia 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. In this context, molecules with high basicity (proton sponges type Poly(amidoamine) - PAMAM and 1,8-bis(dimethylamino)naphthalene - DMAN) could destabilize the tumor metabolism, causing a possible reduction and/or stationary progression of the tumor mass. Compounds with high basicity are usually toxic, however, encapsulation using nanoparticles may decrease the possible toxicity to healthy cells. It is know that the nanoparticles contribute to the selective delivery and biocompatibility through the specific ligands insertion. In this project we focus on the development of pH-sensitive organic-inorganic hybrid nanoparticles capable of loading and protecting active molecules of high basicity, for release in the hypoxic tumor environment. In addition, this chemical therapy through the buffering effect will be combined with gold nanostructures for association with the photo-hyperthermia, making the theranostic system more effective against cancer cells. (AU)