26XZ

Crystal structure of the anti-PEG Fab in complex with PEG fragment OEG13

Summary for 26XZ

• Entry DOI: 10.2210/pdb26xz/pdb
• Descriptor: anti-PEG Fab heavy chain, anti-PEG Fab light chain, DI(HYDROXYETHYL)ETHER (3 entities in total)
• Functional Keywords: anti-peg, fab, antibody, peg-scfv, immune system
• Biological source: Mus musculus; More
• Total number of polymer chains: 4
• Total formula weight: 98814.12

Authors

Xu, Q.,Pan, F.,Yu, Z.,Jiang, K.,Zhan, C.,Ying, T.,Yang, Z. (deposition date: 2026-05-20, release date: 2026-11-11)

Primary citation

Pan, F.,Xu, Q.,Tian, K.,Luo, G.,Qi, Y.,Ma, Y.,Ying, T.,Qian, J.,Yang, Z.,Zhan, C.,Jiang, K.
Anti-PEG Single-Chain Variable-Fragment Antibody-Assisted In Vivo Process Decoding of PEGylated Nanomedicines.
Acs Nano, 20:22215-22232, 2026

PubMed Abstract: Clinical translation of nanomedicines is greatly hindered by insufficient understanding of their in vivo process, yet a key challenge lies in quantifying the encapsulated versus free drug forms in tissues and cells. Herein, we present a facile, versatile anti-PEG single-chain variable-fragment antibody (PEG-scFv)-based method enabling quantitative measurement of both forms in various biofluids (e.g., interstitial fluid, cytoplasm). By this method, we map the in vivo process of PEGylated liposomal doxorubicin (sLip/Dox) at unprecedented resolution. In the bloodstream, doxorubicin remains largely encapsulated in liposomes (>99%). In liver as the main organ for drug elimination, less drug was distributed in the interstitium (>80% encapsulated) but more in liver cells (mainly in Kupffer cells) released in a time-dependent manner, accompanying doxorubicin transferred to hepatocytes most in free form by 12 h postinjection. After extravasation into tumors, there was a limited access of sLip/Dox to tumor cells, confining most of the drug in the interstitium mainly being encapsulated (more than 75%), and the internalized fraction underwent a gradual release process in both tumor-associated macrophages and tumor cells. These findings revealed that for sLip/Dox, which primarily underwent drug release intracellularly, cellular internalization rates could be the key factor in determining its in vivo performance. Given widespread PEGylation on developing nanomedicines and the cost-effectiveness of scFv production, PEG-scFv offers a broadly applicable tool for dissecting in vivo processes of nanomedicines to establish dose-effect relationships like small-molecule drugs, further to guide rational nanotherapeutic design.

PubMed: 42503863
DOI: 10.1021/acsnano.6c09408

Experimental method

X-RAY DIFFRACTION (2.71 Å)