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A covalent tumor-targeted theranostic system for NIR imaging-guided photodynamic-ferroptosis synergistic therapy of lung cancer

Authors: Yurong Fan; Hongyuan Wen; Zhitao Zhu; Chaoxiang Cui; Yuqi Zhang; Zhongsheng Zhao; Miao Li; Yiming Feng; Mei Hu; Xingxiang Ren; Zhengzhong Lv; Zhixin Han; Haibin Shi; Guohua Fan

DOI: 10.1007/s40843-025-4008-2Status: Verified Translated Edition
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Key Findings in This Report

• • dIR-CDF achieves covalent tumor targeting via sulfenic acid-specific reaction, enhancing tumor accumulation and retention; in vivo studies demonstrate efficient NSCLC tumor suppression in living mice, underscoring its clinical potential for precise theranostics. • • The probe enables NIR imaging-guided therapy under 808 nm irradiation, combining photodynamic effect (1O2 generation) with ferrocene-mediated ferroptosis (·OH production via Fenton reaction), synergistically amplifying oxidative damage and lipid peroxidation. • • The system specifically targets integrin αvβ3-positive NSCLC cells, leveraging the overexpression of sulfenated proteins in the tumor microenvironment, which significantly improves specificity over conventional untargeted agents. • • The covalent immobilization strategy, based on 1,3-cyclohexanedione-sulfenic acid reaction, ensures prolonged retention at the tumor site, addressing the bottleneck of rapid clearance and low drug accumulation seen in traditional nanomedicines.