8Z95

Humanized anti-PEG h6.3 Fab in complex with PEG

Summary for 8Z95

• Entry DOI: 10.2210/pdb8z95/pdb
• Descriptor: Heavy chain of Anti-PEG antibody h6-3 Fab fragment, Light chain of Anti-PEG antibody h6-3 Fab fragment, 2,5,8,11,14,17,20,23,26,29,32,35,38,41,44,47,50,53,56,59,62,65,68,71,74,77,80-HEPTACOSAOXADOOCTACONTAN-82-OL, ... (5 entities in total)
• Functional Keywords: anti-peg, fab, immune system
• Biological source: Homo sapiens; More
• Total number of polymer chains: 4
• Total formula weight: 96375.74

Authors

Lin, Y.C.,Chang, C.Y.,Su, Y.C. (deposition date: 2024-04-22, release date: 2025-02-12)

Primary citation

Meng, J.L.,Dong, Z.X.,Chen, Y.R.,Lin, M.H.,Liu, Y.C.,Roffler, S.R.,Lin, W.W.,Chang, C.Y.,Tzou, S.C.,Cheng, T.L.,Huang, H.C.,Li, Z.Q.,Lin, Y.C.,Su, Y.C.
pH-Responsive Polyethylene Glycol Engagers for Enhanced Brain Delivery of PEGylated Nanomedicine to Treat Glioblastoma.
Acs Nano, 19:307-321, 2025

PubMed 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) 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 significantly increased the accumulation of PEGylated nanomedicine in the mouse brain compared to wild-type PEG engager (WT-PEG engager). pH-PEG engager-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 is promising for enhanced brain drug delivery to treat CNS disorders.

PubMed: 39749925
DOI: 10.1021/acsnano.4c05906

Experimental method

X-RAY DIFFRACTION (2.26 Å)