Dual biomarkers-activatable hollow MnO2-Based theranostic nanoplatform for efficient breast cancer-specific multisite fluorescence imaging and synergistic therapy

Background: Theranostic nanoplatforms with integrated diagnostic imaging and multiple therapeutic functions play a vital role in precise diagnosis and efficient treatment for breast cancer, but unfortunately, these nanoplatforms are usually stuck in single -site imaging and single mode of treatment, causing unsatisfactory diagnostic and therapeutic efficiency. Herein, a dual biomarkers-activatable facile hollow mesoporous MnO 2 (H -MnO 2 )- based theranostic nanoplatform, DNAzyme@H -MnO 2 -MUC1 aptamer (DHMM), was constructed for the simultaneous multi -site diagnosis and multiple treatment of breast cancer. Results: The DHMM acted as an integrated diagnostic and therapeutic nanoplatform that realizes multi -site fluorescence imaging -guided high -efficient photothermal/chemodynamic/gene synergistic therapy (PTT/CDT/ GT) for breast cancer. The H -MnO 2 exhibits high loading capacity for Cy5-MUC1 aptamer (3.05 pmoL mu g - 1 ) and FAM-DNAzyme (3.37 pmoL mu g - 1 ), and excellent quenching for the probes. In the presence of MUC1 on the cell membrane and GSH in the cytoplasm, Cy5-MUC1 aptamer and FAM-DNAzyme was activated triggering dualchannel fluorescence imaging at different sites. Moreover, the self -supplied Mn 2 + was further supplied as DNAzyme cofactors to catalytic cleavage intracellular EGR-1 mRNA for high -efficient GT and stimulated the Fenton -like reaction for CDT. The H -MnO 2 also showcases a favorable photothermal performance with a photothermal conversion efficiency of 44.16%, which ultimately contributes to multi -site fluorescence imagingguided synergistic treatment with an apoptosis rate of 71.82%. Significance: This dual biomarker-activatable multiple therapeutic nanoplatform was realized multi -site fluorescence imaging -guided PTT/CDT/GT combination therapy for breast cancer with higher specificity and efficiency, which provides a promising theranostic nanoplatform for the precision and efficiency of breast cancer treatment.