An Experimental Study into the Photodynamic/Sonodynamic Therapy of Triple-Negative Breast Cancer Mediated by the Novel Nano-Photonic Sensitizer NBDPBr Nanoparticles

Purpose: This study aimed to develop a synergistic photodynamic therapy/sonodynamic therapy (PDT/SDT) system that utilises novel NBDPBr nanoparticles (NPs). These NBDPBr NPs are composed of the aza-boron-dipyrromethene (Aza-BODIPY) dye NBDPBr, which is encapsulated in amphiphilic polymer F-127 (Pluronic ® ). The system is intended for the treatment of triple-negative breast cancer (TNBC), and simultaneously establishes a multimodal imaging platform for real-time monitoring of the therapeutic effect. Methods: The photophysical properties of the NBDPBr NPs were characterised. Singlet oxygen ( 1 O 2 ) generation was assessed under laser (L) and ultrasound (US) irradiation. In vitro cytotoxicity and reactive oxygen species (ROS) production were evaluated in 4T1 TNBC cells. The therapeutic effect and biosafety in vivo were tested by using a syngeneic TNBC mouse model, and it was monitored by ultra-resolution micro-imaging (URM) and photoacoustic imaging (PAI). Results: The spherical NBDPBr NPs showed excellent stability, with an average diameter of about 82.9 nm. Combined laser and ultrasound irradiation induced the highest 1 O 2 production, leading to 96.02% cell death in vitro and near-complete tumor suppression in vivo, with no significant systemic toxicity. URM revealed decreased tumor microvascular density and PAI indicated reduced blood oxygen saturation post-treatment, confirming synergistic PDT/SDT-induced vascular disruption and tumor hypoxia. Conclusion: NBDPBr NPs mediate potent synergistic PDT/SDT against TNBC, supported by a dual-modal URM/PAI imaging platform for treatment monitoring. This study presents a promising theranostic strategy with high translational potential for TNBC management. Keywords: photosensitizers, nanoparticle, photodynamic therapy, sonodynamic therapy, triple-negative breast cancer, multimodal imaging, synergistic therapy