Advanced Engineered Nanoplatforms to Overcome Biological Barriers for Targeting Brain Tumors

Effective drug delivery to the brain is critically hindered by the blood-brain barrier (BBB), a selective barrier that complicates treatment for central nervous system (CNS) disorders, including brain tumors. Recent innovations in pharmaceutical sciences have introduced new strategies to surmount this challenge and enhance therapeutic efficacy. This review aims to assess recent advancements in engineered nanoplatforms designed to overcome the BBB, with a focus on their application in brain tumor targeting. It seeks to evaluate different drug delivery strategies and formulations that enhance brain penetration, improve targeting precision, and minimize systemic side effects. A comprehensive review of the literature and recent studies on brain-targeting strategies was conducted. The review examined the strategies to prolong blood circulation time and analyzed particularly the PEGylation approach, lipid-based nanocarrier, albumin binding strategies and red blood cell-based delivery. It also explored various strategies (e.g., peptides, prodrug, antibodies, nanotechnology, ligand-based delivery) and subcellular targeting techniques aimed at enhancing brain drug delivery and cellular uptake. PEGylation was found to significantly improve the ability of nano carriers to penetrate brain tumors by reducing macrophage-mediated clearance. Nanotechnology-based strategies coupled with ligand-based approaches effectively enhance brain delivery. Subcellular targeting strategies facilitated endolysosomal escape, leading to better therapeutic agent retention within brain tumor cells. Advances in nanotechnology and targeting strategies offer promising solutions for overcoming the BBB and improving brain tumor treatment. These novel strategies significantly enhance brain targeting while minimizing systemic effects. Continued research is essential to optimize these methods and achieve more effective therapeutic outcomes.