Photocatalytic Construction of Multivalent Peptide-Human Serum Albumin (HSA) Conjugates Capable of Effectively Attenuating Phagocytosis

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Publication Details

Journal
ACS Applied Materials & Interfaces
Published
2026-09-15
DOI
https://doi.org/10.1021/acsami.6c12040
Primary Topic
Nanoplatforms for cancer theranostics
Type
article
Field-Weighted Citation Impact
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article

Photocatalytic Construction of Multivalent Peptide-Human Serum Albumin (HSA) Conjugates Capable of Effectively Attenuating Phagocytosis

Wen Wen, Xiao‐Peng He, Huisi He, Yong Yu et al.
ACS Applied Materials & Interfaces
Nanoplatforms for cancer theranostics
article

Photocatalytic Construction of Multivalent Peptide-Human Serum Albumin (HSA) Conjugates Capable of Effectively Attenuating Phagocytosis

Wen Wen, Xiao‐Peng He, Huisi He, Yong Yu, Ting-Xuan Chen, Bowen Xu, Hailing Huang, Qiuyun Yi, Hong-Yang Zhang, Xi-Le Hu
article en

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.

ACS Applied Materials & Interfaces
East China University of Science and Technology (CN), University of Shanghai for Science and Technology (CN), Second Military Medical University (CN), Shanghai Changzheng Hospital (CN), Eastern Hepatobiliary Surgery Hospital (CN)
Good health and well-being
Openalex Percentile: Top 20%
Nanoplatforms for cancer theranostics
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