MULTIFUNCTIONAL NANOPARTICLES FOR SITE-ESPECIFIC DELIVERY OF TEMOZOLOMIDE® AND VERTEPORFIN® FOR COMBINATION THERAPY OF BRAIN TUMORS

Abstract

Glioblastoma multiform are one of the most aggressive and mortal human cancers. The most used chemotherapeutic drug for its treatment is Temozolomide (TMZ); however, the blood brain barrier significantly limits its efficacy. A nanostructured material that present the extraordinary characteristic to overcome the blood brain barrier are the micelles based on Pluronic surfactants. In a previous work, we have demonstrated that Pluronic P123/F127 mixed micelles are able to load and stabilize the very hydrophobic drug Verteporfin for visible light therapy application. TMZ have been successfully combined with phototherapies showing synergistic anticancer activity, however clinical trials are still distant due blood brain barrier inhibitory action. Therefore, encapsulate both drugs into Pluronic nanoparticles, especially developed for glioma treatment, is a promising strategy. In addition Pluronic can be synthetically modified in order to insert different functional molecules on its structure as fluorescent probes to tumor imaging and/or targeting agents to increase tumor selectivity. Thus, the aims of the present project are: (i) to develop a multifunctional nanostructured system for TMZ and Verteporfin loading; (ii) optimize the formulation and stability properties of the developed nanoparticle and (iii) demonstrate a significant increase of glioma anticancer activity due the synergistic association of multifunctional nanoparticles and chemo-photodynamic combined therapy.