Supramolecular Nanosystem Based on Pillararene-Capped CuS Nanoparticles for Targeted Chemo-Photothermal Therapy

A smart supramolecular nanosystem integrating targeting, chemotherapy, and photothermal therapy was constructed based on carboxylatopillar[5]­arene (CP[5]­A)-functionalized CuS nanoparticles (CuS@CP NPs). CuS@CP NPs with good monodispersibility and strong near-infrared absorption were synthesized in aqueous solution through a facile one-pot supramolecular capping method, followed by surface installation of a liver cancer-targeted galactose derivative through host–guest binding interaction. The resulting smart supramolecular nanosystem, namely, CuS@CPG, exhibited excellent photothermal ablation capability to HepG2 cells upon irradiation with laser at 808 nm. Chemotherapeutic drug, doxorubicin hydrochloride (DOX), was further loaded on CuS@CPG via electrostatic interactions between positively charged DOX and negatively charged CP[5]­A to give CuS@CPG–DOX with a high drug-loading capacity up to 48.4%. The weakening of DOX–CP[5]­A interactions in an acidic environment promoted the pH-responsive drug release from CuS@CPG–DOX. Significantly, this multifunctional supramolecular nanosystem showed a remarkably enhanced therapeutic effect through the combination of targeted chemotherapy and photothermal therapy upon in vitro cell study. Moreover, preliminary in vivo study demonstrated that CuS@CPG and CuS@CPG–DOX had good biocompatibility and excellent tumor inhibition effects upon near-infrared laser irradiation.