Squaric Acid-Coumarin-Chlorambucil: Photoresponsive Single-Component Fluorescent Organic Nanoconjugates for Self-Monitored Therapeutics

Abstract

In this paper, we have developed photoresponsive fluorescent organic nanoconjugates based on a single-component system for effective cancer treatment by a synergistic combination of photodynamic therapy (PDT) and chemotherapy. Our single-component system was synthesized by coupling the squaric acid and the coumarin-chlorambucil conjugate. Next, multifunctional squaric acid-coumarin-chlorambucil (Sq-Cou-Cbl) nanoconjugates were prepared by “simple reprecipitation technique”. The unique properties of the newly designed Sq-Cou-Cbl nanoconjugates are (i) a phototrigger for controlled anticancer drug (chlorambucil) release and a photosensitizer for PDT upon visible light irradiation (ii) cellular imaging and self-monitoring of the drug release by a noninvasive fluorescent technique and (iii) PDT activity of the released photoproduct thereby resulting in the improved therapeutic efficiency. Further, in vitro studies showed that Sq-Cou-Cbl nanoconjugates exhibited an enhanced anticancer activity by synergistic cytotoxic effect of PDT and chemotherapy on HeLa cells.