Heptazine Based Photo‐Programmable Azobenzene‐Amino Acid Nanotubes for Augmented Drug Delivery and Chemo‐Photodynamic Therapy in Glioma

Heptazine or tri-s-triazine, is one of the oldest known nitrogen-containing heterocycles that kindled a new arena in biomedical research in the recent past due to their rich fascinating properties. Here, we report design and development of self-assembled nano biomaterials consisting of heptazine-derived π-conjugated azobenzene for photo-activated glioma therapy. The model anti-cancer drug, Docetaxel is co-assembled with heptazine-derived π-conjugated Azobenzene and Fmoc-Isoleucine-OH to form stable Tubular nanostructures (Dtx@AI-Ts). Due to the presence of photoisomerizable azobenzene moiety, AI-Ts exhibit a light-induced transformation to nanotubes of lesser dimensions upon 405 nm light irradiation, thereby improving drug release and enhancing their applicability as nano-drug delivery systems. This structural adaptability, coupled with the material's ability to induce reactive oxygen species (ROS) upon light activation, helps to achieve higher therapeutic efficacy against glioma. In vitro therapeutic efficacy investigated in terms of cell viability (MTT assay) and oxidative stress generation demonstrates an enhanced therapeutic outcome with Dtx@AI-Ts in C6 glioma cells. Further, in the C6 syngeneic glioma rat model, a prompted tumor depletion (∼90%) is observed post 21-days of therapy, along with good compatibility toward healthy body organs. Thus, this work establishes the potential of smart self-assembled drug loaded photo-responsive nanomaterials toward enabling advanced glioma treatment.