Authors
Hailing Huang, Ting-Xuan Chen, Bowen Xu, Yong Yu, Huisi He, Qiuyun Yi, Hong-Yang Zhang, Xi-Le Hu, Xiao-Peng He, Wen Wen
Published in
ACS applied materials & interfaces. Sep 15, 2026. Epub Sep 15, 2026.
Abstract
Upon entry into the bloodstream, nanocarriers can be rapidly cleared by the mononuclear phagocyte system (MPS), limiting their clinical translation. In this study, based on the CD47-SIRPα "don't eat me" signaling pathway, we functionalized human serum albumin (HSA) with peptides (SP1) truncated from CD47. Ortho-nitrobenzyl alcohol (o-NBA) was used as a photoreactive handle to modify SP1, and a subsequent photocatalysis gave rise to SP1-HSA conjugates (multi-HSA) with the peptide being multivalently displayed on the albumin. For comparison, a monovalent conjugate (mono-HSA) was prepared via a site-specific thiol-maleimide chemistry at Cys34. Both conjugates were loaded with chlorin e6 (Ce6) for in vitro evaluation and indocyanine green (ICG) for in vivo imaging. We found that multi-HSA@Ce6 reduced macrophagic uptake by ∼8-fold with respect to mono-HSA@Ce6, demonstrating the effectiveness of multivalency. Competitive binding and SIRPα-knockdown assays validated that the CD47-SIRPα signaling pathway mediated the attenuation of macrophagic uptake. In vivo biodistribution studies revealed that multi-HSA@ICG reduced hepatic uptake by ∼2-fold and significantly prolonged blood circulation with respect to unmodified HSA@ICG. This work establishes a facile and effective photocatalytic approach for the construction of multivalent peptide-protein conjugates capable of escaping from phagocytic clearance for drug delivery applications.
PMID:
42742063
Bibliographic data and abstract were imported from PubMed on 15 Sep 2026.
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