Size-Dependent Glioblastoma Targeting by Polymeric Nanoruler with Prolonged Blood Circulation

Size-Dependent Glioblastoma Targeting by Polymeric Nanoruler with Prolonged Blood Circulation

Currently, there is no effective treatment for glioblastoma multiforme (GBM), the most frequent and malignant type of brain tumor. The blood–brain (tumor) barrier (BB­(T)­B), which is composed of tightly connected endothelial cells and pericytes (with partial vasculature collapse), hampers nanomedic...

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Bibliographic Details
Published in:Bioconjugate chemistry Vol. 35; no. 8; pp. 1154 - 1159
Main Authors: Ishibashi, Yukine, Naito, Mitsuru, Watanuki, Yusuke, Hori, Mao, Ogura, Satomi, Taniwaki, Kaori, Cho, Masaru, Komiya, Ryosuke, Mochida, Yuki, Miyata, Kanjiro
Format: Journal Article
Language:English
Published: United States American Chemical Society 21-08-2024
Subjects:
Accumulation
Animals
Bioaccumulation
Blood circulation
Blood-Brain Barrier - metabolism
Brain
Brain cancer
Brain Neoplasms - metabolism
Brain Neoplasms - pathology
Brain tumors
Cell Line, Tumor
Cell size
Copolymers
Downsizing
Endothelial cells
Glioblastoma
Glioblastoma - metabolism
Glioblastoma - pathology
Glioma
Graft copolymers
Humans
Mice
Nanoparticles - chemistry
Nanotechnology
Particle Size
Pericytes
Polyethylene glycol
Polyethylene Glycols - chemistry
Polymers - chemistry
Tissue Distribution
Tumors
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Summary:Currently, there is no effective treatment for glioblastoma multiforme (GBM), the most frequent and malignant type of brain tumor. The blood–brain (tumor) barrier (BB­(T)­B), which is composed of tightly connected endothelial cells and pericytes (with partial vasculature collapse), hampers nanomedicine accumulation in tumor tissues. We aimed to explore the effect of nanomedicine size on passive targeting of GBM. A series of size-tunable poly­(ethylene glycol) (PEG)-grafted copolymers (gPEGs) were constructed with hydrodynamic diameters of 8–30 nm. Biodistribution studies using orthotopic brain tumor-bearing mice revealed that gPEG brain tumor accumulation was maximized at 10 nm with ∼14 dose %/g of tumor, which was 19 times higher than that in the normal brain region and 4.2 times higher than that of 30-nm gPEG. Notably, 10-nm gPEG exhibited substantially higher brain tumor accumulation than 11-nm linear PEG owing to the prolonged blood circulation property of gPEGs, which is derived from a densely PEG-packed structure. 10 nm gPEG exhibited deeper penetration into the brain tumor tissue than the larger gPEGs did (>10 nm). This study demonstrates, for the first time, the great potential of a nanomedicine downsizing strategy for passive GBM targeting.
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ISSN:1043-1802
1520-4812
1520-4812
DOI:10.1021/acs.bioconjchem.4c00235