Rational Design of a Theranostic Agent Triggered by Endogenous Nitric Oxide in a Cellular Model of Alzheimer’s Disease

Oxidative damage caused by upregulated
nitric oxide (NO) plays
an important role in the pathogenesis of Alzheimer’s disease
(AD). Currently, stimulus-triggered theranostic agents have received
much attention due to benefits on disease imaging and targeted therapeutic
effects. However, the development of a theranostic agent triggered
by NO for AD remains unexplored. Herein, through the mechanism analysis
of the reaction between a fluorophore of 9,14-diphenyl-9,14-dihydrodibenzo­[a,c]­phenazine (DPAC) and NO, which we occasionally
found and thereafter structure optimization of DPAC,
a theranostic agent DPAC-(peg)4-memantine was fabricated. In an AD cellular model, DPAC-(peg)4-memantine exhibits NO sensing ability for AD imaging. Meanwhile, DPAC-(peg)4-memantine shows improved therapeutic
by targeted drug release triggered by NO and sustained therapeutic
effects owing to the synergetic antioxidative abilities via the anti-AD
drug and NO scavenging. This work provides an unprecedented avenue
for the studies on not only AD but also other diseases with NO upregulation.