Multifunctional Gold Nanocluster Decorated Metal-Organic Framework for Real-Time Monitoring of Targeted Drug Delivery and Quantitative Evaluation of Cellular Therapeutic Response

摘要

Therapeutic drug monitoring is central to optimize therapeutic efficacy and minimize adverse events; however, the pharmacokinetics and pharmacodynamics of most drugs differ greatly among individuals. Evaluation of the therapeutic response is in urgent need to help clinician predict the clinical dose of drug. Herein, we described an analytical assay using gold nanocluster (AuNC)-decorated metal-organic frameworks (MOFs) for targeted drug delivery and monitoring pharmacodynamics, giving attractive options for studying individualized therapy. The camptothecin (Cam) anticancer drug was caged in the NH2-MIL-101(Fe) MOFs. Modification with pegylated folate (FA) for specifically recognizing a FA receptor on the cancer cell membrane significantly improved the delivery efficiency. Intercellular delivery of Cam initiated programmed death of cells and upregulated the apoptosis indicator (caspase-3), which cleaved the peptide linker between AuNCs and MOFs. The quenched fluorescence of AuNCs was then recovered once the peptide was enzymatically cleaved by caspase-3. Real-time monitoring of targeted drug delivery was achieved by imaging of the light-up fluorescence in HepG2 cells, while the amount of caspase-3 could be quantified by detecting Au in the released AuNCs in inductively coupled plasma mass spectrometry (ICP-MS) with a limit of detection (LOD) of 0.12 ng mL(-1). Our assay emphasizes the application of multifunctional nanomaterial for therapeutic self-monitoring and quantitative evaluation of therapeutic response, allowing the acceleration of drug evaluation.