Albumin-functionalized CuFeS2/photosensitizer nanohybrid for single-laser-induced folate receptor-targeted photothermal and photodynamic therapy.

Multimodal therapy is an emerging medical intervention to overcome the current limitation in cancer therapy combining treatment modalities with different mechanisms of action to eradicate tumors. This study demonstrates a targeted multifunctional bovine serum albumin (BSA)-functionalized CuFeS2/chlorin e6 (Ce6) for synergistic photothermal therapy (PTT) and photodynamic therapy (PDT) effects. The CuFeS2 nanocrystals were synthesized through a simple heating-up approach and transferred into an aqueous phase using BSA in an ultrasonic-assisted microemulsion method. The as-prepared CuFeS2@BSA nanoparticles further conjugated with folic acid (FA) followed by attachment of Ce6 to form the Ce6:CuFeS2@BSA-FA nanohybrid with improved solubility and strong near-infrared (NIR) absorbance and fluorescence. It is the first report to fabricate the targeted Ce6:CuFeS2@BSA-FA hybrid and evaluates their synergistic PTT/PDT effect using a single laser. The Ce6:CuFeS2@BSA-FA hybrid showed lower toxicity in vitro (HeLa and HepG2 cells) and in vivo (zebrafish embryos), while they are selectively recognized and internalized by HeLa cells that over-express folate receptors. Compared to each modality applied separately, the combined single-laser-induced PTT and PDT treatment showed the enhanced generation of heat and reactive oxygen species (ROS) with synergistic cancer killing under 671 nm laser irradiation (10 min, 1 W/cm2). As a biocompatible targeted nanoprobe, the multifunctional nanohybrid holds promise in combined PDT/PTT synergistic therapy to achieve better efficacy.