Metal-polyphenol nanodots loaded hollow MnO2 nanoparticles with a “dynamic protection” property for enhanced cancer chemodynamic therapy

[Display omitted] Chemodynamic therapy (CDT) is a novel cancer therapeutic strategy. However, barriers such as high glutathione (GSH) concentration and low concentration of metal ions intracellular reduce its treatment effect. In this work, a nanosystem named GA-Fe@HMDN-PEI-PEG with a “dynamic protection” property was reported for enhanced cancer CDT. Mesoporous hollow manganese dioxide (MnO2) nanoparticle (HMDN) was prepared to load gallic acid-ferrous (GA-Fe) nanodots fabricated from gallic acid (GA) and ferrous ion (Fe2+). Then the pores of HMDN were blocked by polyethyleneimine (PEI), which was then grafted with methoxy poly(ethylene glycol) (mPEG) through a pH-sensitive benzoic imine bond. mPEG could protect the nanoparticles (NPs) against the nonspecific uptake by normal cells and enhance their accumulation in the tumor. However, in the slightly acidic tumor microenvironment, hydrolysis of benzoic imine led to DePEGylation to reveal PEI for enhanced uptake by cancer cells. The reaction between HMDN and GSH could consume GSH and obtain manganese ion (Mn2+) for the Fenton-like reaction for CDT. GA-Fe nanodots could also offer Fe for the Fenton reaction, and reductive GA could reduce the high-valence ions to low-valence for reusing in Fenton and Fenton-like reactions. These properties allowed GA-Fe@HMDN-PEI-PEG for precise medicine with a high utilization rate and common side effects.