Targeting Glioblastoma: Advances in Drug Delivery and Novel Therapeutic Approaches

Abstract

Glioblastoma (GB) is the most lethal type of primary tumor in the central nervous system. Current treatments include surgical resection followed by chemotherapy and radiotherapy. With this therapeutic regimen, the median survival is less than two years. However, these treatments do not much improve the overall survival of GB patients. GBs are highly angiogenic and invasive tumors and often acquire resistance to therapy. The invasive nature of the disease limits the ability to achieve complete resection of the tumor and the majority of GB patients will experience disease relapse. Moreover, GB is highly heterogeneous, harboring different mutations and presenting different phenotypes. As the brain is considered to be an immune‐privileged tissue, GB is defined as a cold tumor for which current immunotherapies have not yet been demonstrated to improve survival. On top of these challenges, the blood brain barrier (BBB) restricts the uptake of drugs by the brain, thus limiting the therapeutic options. Therefore, enormous efforts are being dedicated to the development of novel nanomedicines, which will be able to cross the BBB and specifically target the cancer cells. Here, the current achievements in drug delivery and novel therapeutic approaches for GB therapy are discussed.

Sulfonated Amphiphilic Poly(α)glutamate Amine—A Potential siRNA Nanocarrier for the Treatment of Both Chemo-Sensitive and Chemo-Resistant Glioblastoma Tumors

“…Furthermore, flow cytometry analysis for SELP expression in U251 cells grown in 2D monolayer or 3D spheroids demonstrated a remarkable increased expression of SELP in the 3D culture (Supplementary Materials Figure S2A). This highlights the importance and the relevance of using SELP as active targeting for the delivery of our polyplexes to GB tumors [28]. The BBB represents a challenge for the delivery of drugs to the brain.…”

“…Furthermore, these micelles selectively delivered siRNA to mammary adenocarcinoma tumors without accumulating in the liver and crossed the dense stroma of PDAC, internalizing into tumor cells and achieving silencing of the target [19]. However, delivery of drugs to the central nervous system (CNS) is extremely difficult since the brain is protected by a highly selective mechanism of capillaries, called the blood-brain barrier (BBB) [28]. Even though brain tumors often display compromised BBB and permeable endothelium, the latter varies with tumor type, location, and prior treatment [29].…”

Neurosurgery at the crossroads of immunology and nanotechnology. New reality in the COVID-19 pandemic

“…Another promising nanopolymeric drug based on a synthetic polymer, N-(2-hydroxypropyl)methacrylamide [281] , conjugated with O-(chloracetyl-carbamoyl) fumagillol (TNP-470) has also been extensively used in preclinical studies including inhibition of GBM growth [282] , [283] . Polymers that deliver drugs to tumors are poorly immunogenic and suitable for multiple treatment, which may be necessary to eradicate the tumor [282] , [284] .…”

Novel Strategies for Nanoparticle-Based Radiosensitization in Glioblastoma

“…In addition, active targeting implies reaching the tumor region, targeting the tumor microenvironment, targeting the vascularization of the tumor microenvironment, or directly targeting tumor cells with internalization, simultaneously considering the route of administration [ 10 ]. Evidently, active targeting involves the use of carriers bearing various surface ligands to achieve either transport across an intact blood–brain barrier (BBB) or cell uptake following extravasation across a leaky BBB [ 15 , 16 , 17 ].…”