Holographically Activatable Nanoprobe via Glutathione/Albumin‐Mediated Exponential Signal Amplification for High‐Contrast Tumor Imaging

• Published in: Advanced materials (Weinheim) 2023-03, Vol.35 (10), p.e2209603-n/a
• Main Authors: Li, Ting, Tan, Shuangxiu, Li, Mengjuan, Luo, Jie, Zhang, Yueyue, Jiang, Zhen, Deng, Yibin, Han, Liang, Ke, Hengte, Shen, Junkang, Tang, Yong'an, Liu, Fan, Chen, Huabing, Yang, Tao
• Format: Article
• Language: English
• Subjects: A549 Cells; Albumins; Albumins - administration & dosage; Albumins - pharmacokinetics; Albumins - pharmacology; Amplification; Animals; Antineoplastic Agents - administration & dosage; Antineoplastic Agents - pharmacokinetics; Antineoplastic Agents - pharmacology; Background noise; Brightening; cancer diagnosis; cascade signal amplification; Cisplatin - administration & dosage; Cisplatin - pharmacokinetics; Cisplatin - pharmacology; Contrast Media - administration & dosage; Contrast Media - pharmacokinetics; Contrast Media - pharmacology; Glutathione; Glutathione - administration & dosage; Glutathione - pharmacokinetics; Glutathione - pharmacology; holographic activation; Holography - methods; Humans; Image Enhancement - methods; Lysosomes - drug effects; Lysosomes - metabolism; Magnetic resonance imaging; Magnetic Resonance Imaging - methods; Manganese; Medical imaging; Metal Nanoparticles - administration & dosage; Mice; Mice, Inbred BALB C; Mice, Nude; Molecular Probes - administration & dosage; Molecular Probes - pharmacokinetics; Molecular Probes - pharmacology; nanoprobe; Neoplasms - diagnostic imaging; Neoplasms - metabolism; Tissue Distribution; Transferrin - administration & dosage; Transferrin - pharmacokinetics; Transferrin - pharmacology; Tumor Microenvironment - drug effects; Tumor Microenvironment - physiology; Tumors
• ISSN: 0935-9648; 1521-4095
• DOI: 10.1002/adma.202209603

Glutathione (GSH)‐activatable probes hold great promise for in vivo cancer imaging, but are restricted by their dependence on non‐selective intracellular GSH enrichment and uncontrollable background noise. Here, a holographically activatable nanoprobe caging manganese tetraoxide is shown for tumor‐selective contrast enhancement in magnetic resonance imaging (MRI) through cooperative GSH/albumin‐mediated cascade signal amplification in tumors and rapid elimination in normal tissues. Once targeting tumors, the endocytosed nanoprobe effectively senses the lysosomal microenvironment to undergo instantaneous decomposition into Mn2+ with threshold GSH concentration of ≈ 0.12 mm for brightening MRI signals, thus achieving high contrast tumor imaging and flexible monitoring of GSH‐relevant cisplatin resistance during chemotherapy. Upon efficient up‐regulation of extracellular GSH in tumor via exogenous injection, the relaxivity‐silent interstitial nanoprobe remarkably evolves into Mn2+ that are further captured/retained and re‐activated into ultrahigh‐relaxivity‐capable complex by stromal albumin in the tumor, and simultaneously allows the renal clearance of off‐targeted nanoprobe in the form of Mn2+ via lymphatic vessels for suppressing background noise to distinguish tiny liver metastasis. These findings demonstrate the concept of holographic tumor activation via both tumor GSH/albumin‐mediated cascade signal amplification and simultaneous background suppression for precise tumor malignancy detection, surveillance, and surgical guidance. A holographically activatable nanoprobe caging manganese tetraoxide is reported for tumor‐selective contrast enhancement in magnetic resonance imaging, which is accomplished through both glutathione/albumin‐mediated cascade signal amplification in tumors and rapid elimination in normal tissues.