Deciphering Nanoparticle Trafficking into Glioblastomas Uncovers an Augmented Antitumor Effect of Metronomic Chemotherapy.

Abstract

Nanoparticles have been explored in glioblastomas as they can traverse the blood-brain barrier and target glioblastoma selectively. However, direct observation of nanoparticle trafficking into glioblastoma cells and their underlying intracellular fate after systemic administration remains uncharacterized. Here, based on high-resolution transmission electron microscopy experiments of an intracranial glioblastoma model, it is shown that ligand-modified nanoparticles can traverse the blood-brain barrier, endocytose into the lysosomes of glioblastoma cells, and undergo endolysosomal escape upon photochemical ionization. Moreover, an optimal dose of metronomic chemotherapy using dual-drug-loaded nanocarriers can induce an augmented antitumor effect directly on tumors, which has not been recognized in previous studies. Metronomic chemotherapy enhances antitumor effects 3.5-fold compared with the standard chemotherapy regimen using the same accumulative dose in vivo. This study provides a conceptual framework that can be used to develop metronomic nanoparticle regimens as a safe and viable therapeutic strategy for treating glioblastomas and other advanced-stage solid tumors.

• Authors: Melgious Jin Yan Ang, Jeehyun Yoon, Mingzhu Zhou, Han-Lin Wei, Yi Yiing Goh, Zhenglin Li, Jia Feng, Haifang Wang, Qianqian Su, Derrick Sek Tong Ong, Xiaogang Liu
• Journal: Advanced materials (Deerfield Beach, Fla.) (Adv Mater) Vol. 34 Issue 3 Pg. e2106194 (Jan 2022) ISSN: 1521-4095 [Electronic] Germany
• PMID: 34726310 (Publication Type: Journal Article)
• Copyright: © 2021 Wiley-VCH GmbH.

Topics

• Blood-Brain Barrier
• Endocytosis
• Glioblastoma (drug therapy)
• Humans
• Nanoparticles (chemistry)