A DNA-MOF hybrid nanosystem for prediction of photodynamic therapy efficacy via amplified imaging of apoptotic mRNA

Photodynamic therapy (PDT) is a promising anticancer treatment modality, however, early evaluation of its therapeutic efficacy remains challenging. Herein, we present a phototheranostic platform that enables in situ monitoring and prediction of PDT efficacy through real-time, amplified imaging of apoptotic mRNA biomarkers. This DNA-MOF nanosystem (denoted as PCN@HCR) integrates of porphyrinic MOFs with DNA-based hybridization chain reaction (HCR) probes, facilitating both efficient PDT and sensitive mRNA detection. In vitro studies showed that PCN@HCR induces irradiation dose-dependent cell apoptosis and specifically detects Bax mRNA through HCR-based signal amplification, revealing a positive correlation between Bax mRNA levels and cell apoptosis. In vivo studies validated that tumor growth was effectively inhibited by PCN@HCR upon lase irradiation, while fluorescent signals of intratumoral Bax mRNA correlated with reduced tumor volumes, confirming the role of Bax mRNA as an potential biomarker for PDT response. This phototheranostic platform offers a promising approach for precise and personalized cancer therapies by providing real-time insights into treatment responses.