A dual-sensitive nanoparticle-mediated synergistic therapy strategy involving photodynamic therapy, chemotherapy and ICD stimuli to treat breast cancer

The combination therapy strategy exerts a significant anti-tumour effect by synergistically eliminating tumour cells through the use of two or more treatments. Nanomedicine delivery systems are widely employed in cancer therapy owing to their ability to effectively improve drug solubility and enhance drug targeting. To this end, we have designed and developed a nano-targeted drug delivery platform PAE-PEG-ss-Ce6/DOX nanoparticles (PPCD NPs), for the co-delivery of the photosensitiser chlorin e6 (Ce6) and the chemotherapeutic agent doxorubicin (DOX). The nanoparticles exhibit a mean particle size of 128.74 ± 0.80 nm, demonstrating excellent serum stability and pH/glutathione (GSH)-responsive release characteristics <i>in vitro</i>. Compared to monotherapy, PPCD NPs exhibited enhanced cytotoxicity and cellular uptake, effectively inhibiting cell proliferation by inducing reactive oxygen species (ROS) production. The results of the immunogenic cell death (ICD) experiments demonstrated that PPCD NPs induced a robust ICD effect through the synergistic action of DOX and Ce6, thereby activating anti-tumour immunity and achieving combination therapy. <i>In vivo</i> experiments and histopathological analysis demonstrated that PPCD NPs exhibit excellent tumour targeting, high anti-tumour efficacy and low biotoxicity. These findings demonstrated the superiority of the phototherapy-chemotherapy-immunotherapy synergistic treatment strategy and indicate that PPCD NPs hold promise as a safe and effective anti-tumour nanoscale targeted drug delivery system.