Visible-Light -Triggered Fluorescent Organic Nanoparticles for Chemo-Photodynamic Therapy with Real-Time Cellular Imaging

In this paper, we have developed a light-activated single component fluorescent organic nanoparticles for synergistic combination therapy (chemo-photodynamic therapy) utilizing the combined benefits of aggregation-induced emission (AIE) and excited-state intramolecular proton transfer (ESIPT) phenomena. The single-component organic nanoparticles were synthesized by coupling tetraphenylethylene (TPE) moiety with the p-hydroxy phenacyl-chlorambucil conjugate. Then, tetraphenylene-p-hydroxyphenacyl-chlorambucil (TPE-pHP-Cbl) nanoparticles were prepared by a simple reprecipitation technique. Our designed TPE-pHP-Cbl NPs exhibited the unique benefits such as (i) aggregation-induced emission enhancement, (ii) large Stoke’s shift, (iii) the photoirradiation wavelength >410 nm, (iv) the drug release occurs only in the aggregated state upon photolysis, (v) PDT activity, (vi) real-time monitoring of drug release by a noninvasive fluorescence color change approach, and (vii) PDT activity of the released photoproduct (TPE-pHP-OH), thereby resulting in the improved therapeutic efficiency. In vitro experiments show that TPE-pHP-Cbl NPs display excellent properties such as cellular imaging, synergistic combination therapy, and biocompatibility.