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Cited 8 time in webofscience Cited 8 time in scopus
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SHMT1 siRNA-Loaded hyperosmotic nanochains for blood-brain/tumor barrier post-transmigration therapy

Authors
Pandey, ShambhaviLee, Myung ChulLim, Jae woonChoung, Yun-HoonJang, Kyoung-JePark, Sang BaeKim, Jae EunChung, Jong HoonGarg, Pankaj
Issue Date
Feb-2022
Publisher
Pergamon Press Ltd.
Keywords
Nanochain; Hyperosmotic; BBB; BTB; Transmigration; NFAT5; Aspect ratio; SHMT1
Citation
Biomaterials, v.281
Indexed
SCIE
SCOPUS
Journal Title
Biomaterials
Volume
281
URI
https://scholarworks.gnu.ac.kr/handle/sw.gnu/1683
DOI
10.1016/j.biomaterials.2021.121359
ISSN
0142-9612
1878-5905
Abstract
The near-perivascular accumulation in solid tumors and short-lived span in circulation, derails even the most competent nanoparticles (NPs) from achieving their maximum therapeutic potential. Moreover, delivering them across the blood brain/tumor barrier (BBB/BTB) is further challenging to sought anticancer effect. To address these key challenges, we designed a linearly aligned nucleic acid-complexed polydixylitol-based polymeric nanochains (X-NCs), with inherent hyperosmotic properties enabling transmigration of the BBB/BTB and navigation through deeper regions of the brain tumor. The high aspect ratio adds shape-dependent functional aspects to parent particles by providing effective payload increment and nuclear factor of activated T cells-5 (NFAT5)mediated cellular uptake. Therefore, serine hydroxymethyltransferase 1 (SHMT1) siRNA-loaded nanochains not only demonstrated to transmigrate the BTB, but also resulted in remarkably reducing the tumor size to 97% in the glioblastoma xenograft brain tumor mouse models. Our study illustrates how the hyperosmotic nanochains with high aspect ratio and aligned structure can accelerate a therapeutic effect in aggressive brain tumors post transmigration of the BBB/BTB by utilizing an NFAT5 mode of uptake mechanism.
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농업생명과학대학 (생물산업기계공학과)
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