MnO2 nanosheet-mediated generalist probe: Cancer-targeted dual-microRNAs detection and enhanced CDT/PDT synergistic therapy

While integrated nanoplatform for diagnosis and therapy has received much recent interest, its widespread application has been hampered by the complicated preparation process, high-cost and low-efficacy. Herein, we designed a MnO2 nanosheet-mediated generalist probe (MNSGP), for intracellular dual-microRNAs (miRNAs) imaging and enhanced synergistic therapy of chemodynamic therapy (CDT) and photodynamic therapy (PDT). Because MNSGP can specifically target nucleolin receptor overexpressed on the cancer cell surface, it can be internalized via a receptor-mediated endocytosis pathway. After entering the cells, MnO2 NS was degraded to Mn2+ by the excessive glutathione (GSH), releasing the DNA probes for cyclic amplification detection of miR-155 and miR-21 based on toehold-mediated strand displacement amplification (TSDA). Meanwhile, the produced O2 by MnO2 NS catalysis can promote the photosensitizer TMPyP4 to produce singlet oxygen (1O2) for PDT. The degraded Mn2+, as Fenton reagent, can convert endogenous H2O2 to cytotoxic hydroxyl radical (·OH) for CDT. In addition, the depletion of GSH impairs the antioxidant defense system (ADS), enhancing the CDT/PDT synergistic effect. The prepared generalist probe was fully characterized. Accuracy of dual-miRNAs detection and the high curative effect of enhanced CDT/PDT synergistic therapy were attested via in vitro and in vivo experiments. Unarguably, MNSGP broadens new horizons in the design of nucleic acid nanoplatform, cancer-targeted detection and theranostic application.