Hollow mesoporous MnO2-carbon nanodot-based nanoplatform for GSH depletion enhanced chemodynamic therapy, chemotherapy, and normal/cancer cell differentiation

A redox-responsive chemodynamic therapy (CDT)-based theranostic system composed of hollow mesoporous MnO2 (H-MnO2), doxorubicin (DOX), and fluorescent (FL) carbon nanodots (CDs) is reported for the diagnosis and therapy of cancer. In general, since H-MnO2 can be degraded by intracellular glutathione (GSH) to form Mn2+ with excellent Fenton-like activity to generate highly reactive .OH, the normal antioxidant defense system can be injured via consumption of GSH. This in turn can potentiate the cytotoxicity of CDT and release DOX. The cancer cells can be eliminated effectively by the nanoplatform via the synergistic effect of chemotherapy and CDT. The FL of CDs can be restored after H-MnO2 is degraded which blocked the fluorescence resonance energy transfer process between CDs as an energy donor and H-MnO2 as an FL acceptor. The GSH can be determined by recovery of the FL and limit of detection is 1.30 mu M with a linear range of 0.075-0.825 mM. This feature can be utilized to efficiently distinguish cancerous cells from normal ones based on different GSH concentrations in the two types of cells. As a kind of CDT-based theranostic system responsive to GSH, simultaneously diagnostic (normal/cancer cell differentiation) and therapeutic function (chemotherapy and CDT) in a single nanoplatform can be achieved.

Automated summary

The redox-responsive chemodynamic therapy system using H-MnO2, DOX, and FL CDs presents a promising approach for cancer diagnosis and treatment by enhancing cytotoxicity through GSH consumption, releasing DOX, and effectively eliminating cancer cells. Additionally, the system can differentiate cancerous cells from normal ones based on GSH concentrations and restore FL after H-MnO2 degradation.