Galactoxyloglucan-Modified Gold Nanocarrier of Doxorubicin for Treating Drug-Resistant Brain Tumors

Abstract

Malignant tumors of central nervous system have the least survival and highest morbidity compared to other prevalent cancers. Being with surgical resection as first-line treatment, further prognosis relies on the consecutive radiotherapy/chemotherapeutic regimen. However, the blood-brain barrier restricts a broad spectrum of chemotherapeutics to reach the tumor microenvironment even at a higher dose of administration. Herein, ultrasmall and spherical gold nanoparticles (GNPs) are capped with an antitumor, tumor necrosis factor-related apoptosis-inducing ligand-targeted galactoxyloglucan PST001 and are employed to enhance the distribution of doxorubicin (DOX) in the brain by crossing the blood–brain barrier. The PST-GNP-DOX NPs exhibit clathrin-mediated cellular internalization and appreciable cytotoxic profile at significantly less half maximal inhibitory concentration concentration. Moreover, higher retention time in plasma, lesser distribution in vital organs, enhanced brain distribution and significant growth inhibition in glioma tumeroid highlights the efficacy in glioma therapy. More importantly, significant downregulation of drug efflux pump and NF-κB evident with a higher cytotoxic profile by PST-GNP-DOX NPs in drug-resistant glioma cells is well-appreciated to mitigate drug-resistant brain tumor.