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In this study, based on the CD47\u2013SIRP\u03b1 \u201cdon\u2019t eat me\u201d 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 \u223c8-fold with respect to mono-HSA@Ce6, demonstrating the effectiveness of multivalency. Competitive binding and SIRP\u03b1-knockdown assays validated that the CD47-SIRP\u03b1 signaling pathway mediated the attenuation of macrophagic uptake. In vivo biodistribution studies revealed that multi-HSA@ICG reduced hepatic uptake by \u223c2-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.<\/jats:p>","DOI":"10.1021\/acsami.6c12040","type":"journal-article","created":{"date-parts":[[2026,9,15]],"date-time":"2026-09-15T11:01:37Z","timestamp":1789470097000},"page":"50533-50542","source":"Crossref","is-referenced-by-count":0,"title":["Photocatalytic Construction of Multivalent Peptide-Human Serum Albumin (HSA) Conjugates Capable of Effectively Attenuating Phagocytosis"],"prefix":"10.1021","volume":"18","author":[{"given":"Hailing","family":"Huang","sequence":"first","affiliation":[{"name":"Third Affiliated Hospital of Naval Medical University (Second Military Medical University) , , ,","place":["Shanghai, China, 200438"]},{"name":"University of Shanghai for Science and Technology , , ,","place":["Shanghai, China, 200093"]},{"name":"Eastern Hepatobiliary Surgery Institute, the Second Military Medical University , , ,","place":["Shanghai, P. 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