Abstract 6382: Temozolomide co-encapsulated radioPDT nanoparticles possess effective cytotoxicity for the treatment of glioblastoma.

Abstract Introduction: Radiation-activated photodynamic therapy (radio-PDT) has emerged as a promising approach to overcome the limitations of conventional photodynamic therapy, particularly the poor tissue penetration of external light sources. This study focuses on the synthesis, characterization, and evaluation of the effect of temozolomide co-encapsulated radio-PDT nanoparticles for the treatment of glioblastoma. Material and Methods: An inorganic nanoscintillator was synthesized, and its comprehensive physicochemical characterization was assessed using electron dispersive x-ray spectroscopy (EDS), Transmission Electron microscopy (TEM), and X-ray diffraction (XRD) to evaluate the evolution of composition, size, and structure. The nanoscintillator was encapsulated with the photosensitizer protoporphyrin IX (PPIX), in combination with Temozolomide (TMZ), in a nanocarrier of PEG-PLGA. The characteristics of nanoparticles was assessed using TEM, Dynamic light scattering (DLS), and zeta potential was recorded. The tumor cytotoxicity of these nanoparticles was evaluated in vitro by using the U251 cell line. Furthermore, the molecular mechanism was elucidated using western blot. Results: Our results showed the size of 15±5 for nanoscentilator, which was encapsulated with PPIX and temozolomide in the nanocarrier PEG-PLGA. The final nanocomposite was 100±10 with a Zeta potential (ZP) of -21.5. These nanoparticles demonstrated significant cytotoxicity against tumor cells compared to the control condition. Western blot analysis showed, decrease in the expression of AKT, PERK, and BCL2, while an increased expression of cleaved caspase 3 in radioPDT and TMZ Co-encapsulated radioPDT with a low dosage of irradiation. Conclusion: Our results support the use of TMZ Co-encapsulated radioPDT and radioPDT with radiation can be used as an efficient approach for deep-seated tumors in particularly radio-resistant glioblastoma. These nanoparticles exhibited excellent biocompatibility, effective cytotoxicity towards tumor cells, and potential for translation into an in vivo tumor study. Citation Format: Muhammad Rafiq, Deepak Dinakaran. Temozolomide co-encapsulated radioPDT nanoparticles possess effective cytotoxicity for the treatment of glioblastoma [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2026; Part 1 (Regular Abstracts); 2026 Apr 17-22; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2026;86(7 Suppl):Abstract nr 6382.