Biodegradable Manganese-Containing Mesoporous Silica Nanoparticles for Precisely Controlled Quercetin Delivery

For most degradable nanocarriers, precisely controlled delivery remains a challenge because the drug release is fast in neutral buffer solution. The unfavorable drug leakage could lead to serious toxicity. Thus, it is important to realize precise controlled delivery for nanocarriers with fast biodegradability but excellent stability in a neutral physiological environment. Here, a biodegradable pH/redox-responsive drug delivery system, quercetin (Que)-loaded and poly(ethylene glycol) (PEG)-modified manganese (Mn)-containing mesoporous silica nanoparticles (MSN), designated as PEG@MSN(Mn)@Que, was built for cancer therapy. Nanoparticles present a rough nanoscale spherical morphology with an average size of 107.2 nm and an ordered mesoporous structure. Quercetin has been successfully loaded with an efficiency of 46.47% and a drug release rate of 48.64%. Mn–O bonds were formed by doping Mn to the MSN framework at the molecular level, and the Mn-doping amount was 36.59%. The pH/redox-responsive cleavage of Mn–O bonds promotes the specific biodegradation of PEG@MSN(Mn)@Que and the controlled Que release in the tumor microenvironment. Especially, the degradation behaviors showed excellent stability of PEG@MSN(Mn)@Que in neutral conditions for 5 days, and the drug leakage was very low (only 5.65% of Que released), achieving the precisely controlled Que delivery. A high antitumor effect was simultaneously achieved by anticancer drug delivery mediated by PEG@MSN(Mn)@Que, and the high biocompatibility of nanoparticles was systematically demonstrated in vitro and in vivo . This work provides a feasible way to reduce side effects caused by drug leakage, improving the antitumor effect.