蘇昱誠副教授研究團隊發表研究成果於ACS Nano
連結網址： https://pubmed.ncbi.nlm.nih.gov/39749925/
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 engagerTfR) 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 engagerTfR significantly increased the accumulation of
PEGylated nanomedicine in the mouse brain compared to wild-type PEG engagerTfR
(WT-PEG engagerTfR). pH-PEG engagerTfR-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 engagerTfR is promising for enhanced brain drug delivery to treat CNS
disorders.
