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Nanomedicine for treatment of glioblastoma : Local and targeted delivery of nanomedicines for the treatment of glioblastoma- Veronique Preat -University of Louvain, Belgium

Veronique Preat

Glioblastoma (GBM) treatment includes, when possible, surgical resection of the tumor followed by chemoradiotherapy, but the survival remains low mainly due to local recurrences. The local and targeted systemic delivery of anticancer drugloaded nanomedicines to treat GBM after surgical resection of the tumor is a promising strategy. Among the strategies that have been adopted in the last two decades to find new and efficacious therapies for the treatment of GBM, the local delivery of chemotherapeutic drugs in the tumor resection cavity emerged. We developed two formulations of anticancer nanomedicines that can be injected peri-surgically in the resection cavity of orthotopic GBM. Both PEG-DMA photopolymerizable hydrogel containing Paclitaxel loaded nanoparticles and lauryl-Gemcitabine lipid nanocapsules that spontaneously form a gel significantly improved the survival of the GBM-bearing mice. Another nanomedicine-based strategy could also improve GBM outcome. Targeted nano-theranostics are promising multifunctional system characterized by nanosize, possibility of surface functionalization, diagnostic and therapeutic capabilities. Due to the loss of BBB integrity in the GBM area, we showed that active targeting or magnetic targeting of SPIO/paclitaxel loaded nanoparticles enhanced the biodistribution of the nanoparticles in the brain and enhanced the survival time of GBM bearing mice after IV administration. The potential of other nanomedicine-based treatments of GBM will be discussed. Glioblastoma or glioblastoma multiforme (GBM) is a highly malignant form of glioma, which is the tumor associated with neoplastic glial cells in the brain, including oligo dendrocytes, astrocytes, and ependymal cells. According to the World Health Organization (WHO), GBM is classified as a grade IV brain tumor, which is the most aggressive variation of the malignancies of the central nervous system (CNS) . GBM is also one of the most prevalent malignant brain tumors, with an incidence rate of about 3.19 per 100,000 people per annum . The etiology of GBM remains unknown, although one of the identified risk factors is the abnormal exposure to ionizing radiation . This disease has a complex genetic expression, including gains of chromosomes 7 and 19, losses of chromosomes 10 and 13, amplification of epidermal growth factor receptor (EGFR) and MDM2, mutation of PTEN, NF1, PDGFRA1, IDH1/2, and deletion of CDKN2A/B. Moreover, the histological characteristics of GBM are quite as diverse as its genetic expression, including increasing mitotic and cellular activity, significant angiogenesis, and necrosis. The shape and size of tumor cells are also highly variable, thus the term multiforme]. GBM invades within the CNS and rarely metastasizes to distant regions . The common symptoms associated with GBM are headaches, cognitive impairment and personality changes, gait imbalances, incontinence, sensory loss, visual disturbances, seizures, confusion, and delirium. Most of the symptoms are nonspecific, therefore, the disease has the risk to be misdiagnosed as other neurological or psychological disorders, such as dementia, epilepsy, or stroke .