Nanoparticle-based Cerebral Drug-Delivery Systems and Antiangiogenic Approach in Gliomas Treatment

Giuseppe      Raudino; Mariella      Caffo; Gerardo      Caruso; Concetta      Alafaci; Francesco      Tomasello

Abstract

The efficacy of current anti-cancer multimodal therapeutic strategies in gliomas is limited by the lack of specific therapies against malignant cells and the prognosis in patients affected by cerebral gliomas remains very unfavorable. Glial tumors seem to be able to create a favorable environment for the invasion of neoplastic cells when they combine with the extracellular matrix through the up-regulation of crucial pathways such as angiogenesis and invasion. The major problem in brain drug delivery is the presence of the blood brain barrier which limits the delivery of many chemotherapeutic agents and other kinds of therapeutic molecules. This event often contributes to the failure of the treatment. Nanoparticle systems can represent ideal devices for delivery of specific compounds to brain tumors across the blood brain barrier. The specificity of hybridization makes antisense method an interesting strategy to selectively modulate the expression of genes involved in tumorigenesis. In this review we will focus on the mechanisms of angiogenesis into gliomas, their importance into tumor progression and the possibilities to block these mechanisms with new nanoparticle-based therapeutic strategies. We will also report the results of preclinical and/or clinical studies that adopt nanoparticle-based antiangiogenic therapeutic approach in cerebral gliomas, considering also some patents deal with antiangiogenic strategy.

Keywords: Antisense therapy, blood brain barrier, angiogenesis, gliomas treatment, nanoparticle systems, Cerebral Drug-Delivery, Antiangiogenic, Glioblastoma multiforme, anaplastic astrocytomas, Malignant gliomas, infiltrate brain tissue, gliomagenesis, proangiogenic, degree of malignancy