Activatable smart nanoprobe for sensitive endogenous MMP2 detection and fluorescence imaging-guided phototherapies

Abstract

A stimuli-activatable theranostic system enabling selective imaging and controlled phototherapies is highly essential for precise cancer diagnosis and treatment. Herein, we designed a smart theranostic nanoprobe that comprised a photosensitizer (PS), gold nanorods (AuNRs) and a matrix metalloproteinase 2 (MMP2)-responsive peptide linker. Apart from being applied for photodynamic therapy (PDT), PS has also been widely used for fluorescence imaging. Spatiotemporal control of the photoactivity of PS is of great importance for cancer theranostics. In the present work, due to the presence of Förster resonance energy transfer (FRET) between PS and AuNRs, the fluorescence and ¹O₂ production of PS were suppressed during the circulation, avoiding adverse damage to normal tissues; however, the nanoprobe could be activated for targeted imaging and selective PDT when the peptide linker was cleaved by overexpressed MMP2 in cancer cells. More importantly, the restored fluorescence could be successfully used to quantitatively detect MMP2 with a detection limit of 29 pM and to light up cancer cells, further guiding synergistically activated PDT/PTT (photothermal therapy) for highly efficient and special killing of cancer cells. This study can help design smart cancer-related biomarker-activatable theranostic probes for molecular sensing and site-specific cancer treatment.