Photosensitive composite nanoparticles adsorbing p-sh <i>BLM</i> for the synergistic therapy of neuroblastoma

Photodynamic therapy (PDT) represents a promising noninvasive modality for the selective targeting of tumors. However, its clinical utility is often constrained by the aggregation-induced quenching of photosensitizers and suboptimal reactive oxygen species (ROS) generation. In contrast, gene therapy has exhibited potent antitumor efficacy through the specific silencing of oncogenic targets. In this study, we developed a cationic photosensitizer-based nanocarrier, PEI-PEG-PpIX, designed to deliver the shRNA-<i>BLM</i> plasmid (p-sh<i>BLM</i>). The PEI-PEG-PpIX/p-sh<i>BLM</i> complex demonstrated a threefold increase in ROS production compared to free PpIX, along with a 57.5% enhancement in transfection efficiency. When this method was combined with photodynamic therapy for the treatment of neuroblastoma, the system significantly suppressed tumor cell proliferation, resulting in an 83.67% tumor growth inhibition rate in murine models. This outcome effectively demonstrates the synergistic integration of gene therapy and photodynamic therapy. Furthermore, the multifunctional nature of this platform enables real-time tumor imaging, thereby facilitating image-guided diagnosis and therapeutic monitoring. Overall, this strategy presents a noninvasive, efficient, and targeted approach to cancer treatment, offering valuable insights for future translational applications.