Nanoplatform based on GSH-responsive mesoporous silica nanoparticles for cancer therapy and mitochondrial targeted imaging.

Mitochondria, as the energy factory of most cells, are not only responsible for the generation of adenosine triphosphoric acid (ATP) but also essential targets for therapy and diagnosis of various diseases, especially cancer. The safe and potential nanoplatform which can deliver various therapeutic agents to cancer cells and mitochondrial targeted imaging is urgently required. Herein, Au nanoparticles (AuNPs), mesoporous silica nanoparticles (MSN), cationic ligand (triphenylphosphine (TPP)), doxorubicin (DOX), and carbon nanodots (CDs) were utilized to fabricate mitochondrial targeting drug delivery system (denoted as CDs(DOX)@MSN-TPP@AuNPs). Since AuNPs, as the gatekeepers, can be etched by intracellular glutathione (GSH) via ligand exchange induced etching process, DOX can be released into cells in a GSH-dependent manner which results in the superior GSH-modulated tumor inhibition activity. Moreover, after etching by GSH, the CDs(DOX)@MSN-TPP@AuNPs can serve as promising fluorescent probe (λex = 633 nm, λem = 650 nm) for targeted imaging of mitochondria in living cells with near-infrared fluorescence. The induction of apoptosis derived from the membrane depolarization of mitochondria is the primary anti-tumor route of CDs(DOX)@MSN-TPP@AuNPs. As a kind of GSH-responsive mitochondrial targeting nanoplatform, it holds great promising for effective cancer therapy and mitochondrial targeted imaging. The mitochondrial targeting drug delivery system was fabricated by AuNPs, MSN, TPP, and CDs. The nanoplatform can realize redox-responsive drug delivery and targeted imaging of mitochondria in living cells to improve the therapeutic efficiency and security.

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 µM 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. The redox-responsive chemodynamic therapy (CDT)-based theranostic system is fabricated by H-MnO2, DOX, and fluorescent CDs. The nanoplatform can realize simultaneously diagnostic (normal/cancer cell differentiation) and therapeutic function (chemotherapy and CDT) to improve the therapeutic efficiency and security.