Targeted delivery of nanomedicines to glioblastoma: Overcoming the clinical barrier
Aadya Nayak, Neerada Meenakshi Warrier, Rachana Raman, V.K. Prabhu, Praveen Kumar
Abstract
The current standard therapy for GBM includes maximal surgical resection, followed by concurrent radiotherapy and oral chemotherapy; however, the median post-diagnosis survival period is only 15–18 months. Nanoparticles (NPs) and their composite drug delivery systems (DDSs)—particularly those with liposomes and polymeric nanoparticles (PNPs)—have become an increasingly popular route for therapeutic delivery in glioblastoma multiforme (GBM). These systems also have the added benefit of enabling combinational therapies, which is particularly necessary for more resilient cancers like GBM. To ensure the most effective means of targeting the tumor microenvironment (TME), GBM stem cells (GSCs) can be used, both as therapeutic targets and as delivery vectors—both avenues showing promising results. However, DDSs directed towards the brain must overcome many barriers associated with cranial administration—including the blood-brain-barrier (BBB) and its derivatives, intracranial fluid pressure, induced regression from NP activating protocols involving heat or electromagnetic radiation, and extended retention of synthetic DDSs within cranial tissue—before they can finally circulate in the clinical domain. In this article, we review the progress made in incorporating GSCs within DDSs design, as well as the challenges that need to be addressed to facilitate a widespread regimen of successfully treating GBM.