Molecular Targets and Nanoparticulate Systems Designed for the Improved Therapeutic Intervention in Glioblastoma Multiforme

Abstract

Glioblastoma multiforme (GBM) is the most aggressive and fatal CNS related tumors, which is responsible for about 4% of cancer-related deaths. Current GBM therapy includes surgery, radiation, and chemotherapy. The effective chemotherapy of GBM is compromised by two barriers, i. e., the blood-brain barrier (BBB) and the blood tumor barrier (BTB). Therefore, novel therapeutic approaches are needed. Nanoparticles are one of the highly efficient drug delivery systems for a variety of chemotherapeutics that have gained massive attention from the last three decades. Perfectly designed nanoparticles have the ability to cross BBB and BTB and precisely deliver the chemotherapeutics to GBM tissue/cells. Nanoparticles can encapsulate both hydrophilic and lipophilic drugs, genes, proteins, and peptides, increase the stability of drugs by protecting them from degradation, improve plasma half-life, reduce adverse effects and control the release of drugs/genes at the desired site. This review focussed on the different signaling pathways altered in GBM cells to understand the rationale behind selecting new therapeutic targets, challenges in the drug delivery to the GBM, various transport routes in brain delivery, and recent advances in targeted delivery of different drug and gene loaded various lipidic, polymeric and inorganic nanoparticles in the effective management of GBM.

Development, Characterization, and Evaluation of α-Mangostin-Loaded Polymeric Nanoparticle Gel for Topical Therapy in Skin Cancer

“…This technology utilizes polymer nanoparticles (NPs) that allow the primary drug to reach the targeted region using a delivery vehicle that is versatile, biocompatible, biodegradable, and nanosized. In cancer, prolonged circulation of NPs enriches drug availability to the tumor tissues through direct permeation and diffusion to the cells or enhanced permeation and retention effects [ 9 , 10 , 11 , 12 ]. The transport of NPs across distinguished skin layers may face difficulty in permeation and penetration, probably due to the hard and horny multilayer of stratum corneum, followed by dermis barriers.…”

Emodin-Conjugated PEGylation of Fe3O4 Nanoparticles for FI/MRI Dual-Modal Imaging and Therapy in Pancreatic Cancer

“…40 Considering the abovementioned differences, the EPR effect may occur by allowing selective targeting to TME. [41][42][43] EPR effect is one of the most widely used mechanisms for passive targeting of NPs to solid tumors. Obviously, leaky vasculature and the EPR effect might allow fractional accumulation of NPs in the tumor tissue and consequently facilitate in fulfilled treatments.…”

“Compoundless Anaesthesia”, Controlled Administration, and Post-Operative Recovery Acceleration: Musings on Theoretical Nanomedicine Applications

“…These questions are, in part, spawned due to the uncertainty surrounding the safety of manipulating the BBB, and whether its structure can be harmlessly manipulated with the same methods that would be employed for ECM penetration. They also arise because of the differences in function between the BBB and ECM, and traditional concerns regarding the precision delivery of compounds across the BBB and underlying support structures even if they are proving effective in recent research [ 59 , 60 , 61 ]. While the resolution of these questions and concerns may seem simple to address, reality reminds us that the procedures set out in internal review boards and medical ethics committees necessitate that proper safety measures are implemented for research of this nature because of the potential for harm that may result in permanent BBB damage or miscalculations into hyper-tuned haematic manipulation.…”