pH-Responsive Polyethylene Glycol Engagers for Enhanced Brain Delivery of PEGylated Nanomedicine to Treat Glioblastoma

IF 15.8 1区材料科学 Q1 CHEMISTRY, MULTIDISCIPLINARY

ACS Nano Pub Date : 2025-01-03 DOI:10.1021/acsnano.4c05906

Jun-Lun Meng, Zi-Xuan Dong, Yan-Ru Chen, Meng-Hsuan Lin, Yu-Ching Liu, Steve R. Roffler, Wen-Wei Lin, Chin-Yuan Chang, Shey-Cherng Tzou, Tian-Lu Cheng, Hsiao-Chen Huang, Zhi-Qin Li, Yen-Cheng Lin, Yu-Cheng Su

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引用次数: 0

Abstract

The blood–brain barrier (BBB) remains a major obstacle for effective delivery of therapeutics to treat central nervous system (CNS) disorders. Although transferrin receptor (TfR)-mediated transcytosis is widely employed for brain drug delivery, the inefficient release of therapeutic payload hinders their efficacy from crossing the BBB. Here, we developed a pH-responsive anti-polyethylene glycol (PEG) × anti-TfR bispecific antibody (pH-PEG engager^TfR) that can complex with PEGylated nanomedicine at physiological pH to trigger TfR-mediated transcytosis in the brain microvascular endothelial cells, while rapidly dissociating from PEGylated nanomedicine at acidic endosomes for efficient release of PEGylated nanomedicine to cross the BBB. The pH-PEG engager^TfR significantly increased the accumulation of PEGylated nanomedicine in the mouse brain compared to wild-type PEG engager^TfR (WT-PEG engager^TfR). pH-PEG engager^TfR-decorated PEGylated liposomal doxorubicin exhibited an enhanced antitumor effect and extended survival in a human glioblastoma (GBM) orthotopic xenograft mice model. Conditional release of PEGylated nanomedicine during BBB-related receptor-mediated transcytosis by pH-PEG engager^TfR is promising for enhanced brain drug delivery to treat CNS disorders.

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来源期刊

ACS Nano 工程技术-材料科学：综合

CiteScore

26.00

自引率

4.10%

发文量

1627

审稿时长

1.7 months

期刊介绍： ACS Nano, published monthly, serves as an international forum for comprehensive articles on nanoscience and nanotechnology research at the intersections of chemistry, biology, materials science, physics, and engineering. The journal fosters communication among scientists in these communities, facilitating collaboration, new research opportunities, and advancements through discoveries. ACS Nano covers synthesis, assembly, characterization, theory, and simulation of nanostructures, nanobiotechnology, nanofabrication, methods and tools for nanoscience and nanotechnology, and self- and directed-assembly. Alongside original research articles, it offers thorough reviews, perspectives on cutting-edge research, and discussions envisioning the future of nanoscience and nanotechnology.