上海科技大学知识管理系统

The five-year survival rate of hepatocellular carcinoma(HCC) remainsunsatisfactory. This reflects, in part, the paucity of effective methodsthat allow the target-specific diagnosis and therapy of HCC. Here,we report a strategy based on engineered human serum albumin (HSA)that permits the HCC-targeted delivery of diagnostic and therapeuticagents. Covalent cysteine conjugation combined with the exploitationof host-guest chemistry was used to effect the orthogonal functionalizationof HSA with two functionally independent peptides. One of these peptidestargets glypican-3 (GPC-3), an HCC-specific biomarker, while the secondreduces macrophage phagocytosis through immune-checkpoint stimulation.This orthogonally engineered HSA proved effective for the GPC-3-targeteddelivery of near-infrared fluorescent and phototherapeutic agents,thus permitting target-specific optical visualization and photodynamicablation of HCC in vivo. This study thus offers new insights intospecificity-enhanced fluorescence-guided surgery and phototherapyof HCC through the orthogonal engineering of biocompatible proteins.