Precision photodamage of RNA and mitochondria for cancer therapy with upconversion nanoparticles

Photodynamic therapy (PDT) is an emerging approach for cancer treatment that circumvents the discomfort associated with surgical interventions; however, its therapeutic effectiveness remains constrained. In this study, an innovative nanoplatform is introduced that is designed to enhance the efficacy of PDT by specifically targeting RNA and mitochondria, along with providing real-time in vivo imaging capabilities. The nanoplatform is constructed from a multifunctional nanocomposite, UCNP@PEI-RB-furan (referred to as UPRf), integrates several critical components: upconversion nanoparticles (UCNPs) to facilitate light penetration into deep tissue, Rose Bengal (RB) to generate reactive oxygen species (ROS) including singlet oxygen (¹O₂) for cancer cell destruction, a furan moiety for RNA crosslinking in the presence of ¹O₂, and polyethylenimine (PEI) for electrostatically binding to mitochondria. This design offers multiple benefits, including the absence of phototoxicity in sunlight since PDT is activated by near-infrared (NIR) light, significant cell destruction by targeting the energy-producing organelles-mitochondria, and disruption of cellular function through damage to cytoplasmic RNA. The findings show that the nanoplatform achieved remarkable cancer regression both in vitro and in vivo, outperforming non-targeting alternatives.