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.