Self-assembled hybrid nanotubes for x-ray activated photodynamic therapy (X-PDT) on brain cancer

Photodynamic therapy (PDT) is an alternative tumor-ablative and function-sparing oncologic intervention. PDT involves three components: light, oxygen, and a phototosensitizer, which produces upon photoactivation reactive oxygenated species (ROS), or singlet oxygen (SO). These moieties are responsible for the cell-killing and therapeutic effects. Despite its proved efficiency, the use of PDT is actually limited to superficial and flat lesions, because of the tissue-penetration depth limit of visible photons required by conventional photosensitizers. A potential solution is the use of scintillating nanoparticles to activate the SO sensitizers. The large penetration depth of x-rays removes the limit for the application of PDT in deep tissues. Upon excitation by ionizing radiation, light is generated by the nanoparticles and activates the photosensitizers through energy transfer to produce SO.[1] The radiation and photodynamic therapies are therefore combined and occur simultaneously, leading to a more efficient tumor destruction. Here, it is shown how hybrid fluorescent nanotubes can serve as X-PDT agents for targeting and treatment of brain cancer. An ionic self-assembly strategy is used to functionalize the surface of synthetic chrysotile scintillating mineral nanotubes with efficient SO-sensitizer organic dyes. The dye fluorescence properties are preserved from the in vitro to the in vivo condition, and functionalized nanotubes show the ability to migrate across the blood brain barrier, thus reaching the brain tumor after injection.[2] Upon x-ray irradiation, the hybrid nanotubes work effectively as SO sensitizers inducing cellular death. Encouraging tests conducted on human-derived glioblastoma neurospheres highlight the potential of these multicomponent nanomaterials for brain cancer treatment. The simplicity of the synthesis route combined with their affinity with the in vivo condition strongly support their development as effective functional materials for broader application in the biomedical field. [1] H. Chen et al. Nano Lett. 2015, 15, 2249 [2] C. Villa et. al. Adv. Funct. Mater. 2018, 1707582