Journal
ADVANCED MATERIALS
Volume 34, Issue 3, Pages -Publisher
WILEY-V C H VERLAG GMBH
DOI: 10.1002/adma.202106194
Keywords
anti-angiogenesis; anti-glioma effect; blood-brain barrier; glioblastoma; metronomic chemotherapy; nanoparticles
Categories
Funding
- Singapore Ministry of Education [MOE2017-T2-2-110]
- Agency for Science, Technology and Research (A*STAR) [A1883c0011, A1983c0038]
- National Research Foundation, Prime Minister's Office, Singapore [NRF-NRF105-2019-0003]
- National Basic Research Program of China [2016YFA0201600]
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Nanoparticles modified with ligands can cross the blood-brain barrier, endocytose into the lysosomes of glioblastoma cells, and undergo endolysosomal escape under photochemical ionization. Metronomic chemotherapy using dual-drug-loaded nanocarriers can induce an enhanced antitumor effect 3.5 times greater than standard chemotherapy.
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.
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