| خلاصه مقاله | Background:
Glioblastoma (GBM) is a highly aggressive brain tumor with poor prognosis due to the limitations of the blood-brain barrier (BBB) and the blood-brain tumor barrier (BBTB), which restrict effective chemo-drugs delivery into the brain parenchyma. Furthermore, the formation of a protein corona (PC) around nanoparticles (NPs) in biological fluids can hinder targeting and lead to off-target ratio enhancement. This study aims to design a dual-targeted nanoparticle system capable of crossing brain barriers while addressing PC-related challenges.
Materials and Method:
Chitosan NPs were modified with D8 and RI-VAP peptides to facilitate BBB penetration and glioma targeting, respectively. NPs were characterized by dynamic light scattering (DLS), scanning electron microscopy (SEM), and zeta potential. PC formation was assessed by SDS-PAGE experiment, and different ligand ratios were optimized to minimize undesired protein adsorption. In vivo BBB and BBTB penetration were evaluated in an orthotopic C6 glioma rat model using fluorescence imaging (microscopy and in vivo imaging system).
Results:
The dual-modified NPs demonstrated favorable physicochemical properties and stability. Also, optimized ligand presentation reduced nonspecific protein adsorption and preserved targeting efficacy. Furthermore, the engineered NPs effectively crossed both BBB and BBTB, accumulating predominantly in tumor site, in vivo. Reduced off-target organ biodistribution confirmed the role of controlled PC formation in enhancing specificity, in ligands ratio dependent manner.
Conclusion:
This study presents a rationally designed dual-targeted NP platform that overcomes major biological barriers in glioblastoma therapy. By addressing both brain barriers penetration and PC interference, this system improves targeted delivery and holds promise for future clinical application in central nervous system (CNS) tumors. |