Visible Light-Responsive Delivery of Two Anticancer Drugs Using Single-Component Fluorescent Organic Nanoparticles

Combination therapy is a promising strategy to improve therapeutic efficiency and minimize side effects. So far, the C9-functionalized acridine derivatives were employed as photocages to deliver only one active molecule. Here, we have developed a C4, C5-substituted dual-arm acridine photocage for the first time to release two carboxylic acids and amino acids simultaneously. As a proof of concept, we have constructed a visible light-responsive dual drug delivery system (Acr-Cbl-Vpa) and made it single-component fluorescent organic nanoparticles (NPs) to deliver two anticancer drugs (chlorambucil and valproic acid). Acr-Cbl-Vpa NPs can accumulate inside the cell nucleus, and the planer motif allows the photocage to intercalate with the DNA and maximize the cancer cell killing ability of the drugs. In vitro studies with cancerous HeLa cell lines showed that Acr-Cbl-Vpa NPs displayed improved anticancer efficacy and real-time fluorescence monitoring of the drug release.