Using host–guest interactions at the interface of quantum dots to load drug molecules for biocompatible, safe, and effective chemo-photodynamic therapy against cancer

Abstract

Combining photodynamic therapy (PDT) and chemotherapy (CHT) by loading an anti-cancer drug and a photosensitizer (PS) into the same delivery nanosystem has been proposed as an effective approach to achieve synergistic effects for a safe cancer treatment. However, exploring an ideal delivery nanosystem has been challenging, because the noncovalent interactions must be maintained between the multiple components to produce a stable yet responsive nanostructure that takes into account the encapsulation of drug molecules. We addressed this issue by engineering the interfacial interaction between Ag₂S quantum dots (QDs) using a pillararene derivative to direct the co-self-assembly of the entire system. The high surface area-to-volume ratio of the Ag₂S QDs provided ample hydrophobic space to accommodate the anti-drug molecule doxrubicine. Moreover, Ag₂S QDs served as PSs triggered by 808 nm near-infrared (NIR) light and also as carriers for high-efficiency delivery of drug molecules to the tumor site. Drug release experiments showed smart drug release under the acidic microenvironments (pH 5.5) in tumor cells. Additionally, the Ag₂S QDs demonstrated outstanding PDT ability under NIR light, as confirmed by extracellular and intracellular reactive oxygen species generation. Significant treatment efficacy of the chemo-photodynamic synergistic therapy for cancer using the co-delivery system was demonstrated via in vitro and in vivo studies. These findings suggest that our system offers intelligent control of CHT and PDT, which will provide a promising strategy for constructing hybrid systems with synergistic effects for advanced applications in biomedicine, catalysis, and optoelectronics.