Synergetic effect of a laser-activated nanocomposite for GBM therapy

Glioblastoma (GBM) is regarded as one of the most lethal human cancers. Despite recent progress in cancer therapy, it has remained an incurable disease. Thus, novel approaches are welcome to envision new protocols that improve current treatments to prolong patients' lives. Here, a novel nano-drug system is developed alongside selective chemotherapy accompanied by photodynamic therapy (PDT). The proposed nanocomposite (NCP) is composed of a targeting agent (fluoxetine), a chemotherapeutic drug (temozolomide), a photosensitizer (methylene blue), and zinc oxide nanoparticles (ZnO NPs). The system relies on ZnO NPs as nanocarriers that gradually release temozolomide (TMZ) in PBS at a pH of 7.4. The characterization of the synthesized NCP was carried out using manifold techniques (e.g., transmission electron microscopy (TEM), X-ray diffraction (XRD), and energy-dispersive X-ray spectroscopy (EDS)). Moreover, the NCP cytotoxicity is assessed by the MTT method, and the cellular uptake efficacy is analyzed using flow cytometry. The release amount is measured to be 15 % at 120 h to mitigate the intake of higher doses. The significant PDT parameters have been systematically determined, including the extinction coefficient (&epsi) through modified Beer-Lambert (MBL), quantum yield (η_f), as well as the content of reactive oxygen species (ROS. Although the NCP's quantum yield (η_f = 0.24) is reduced by half against that of the MB (η_f = 0.52), the parameter of ε notably elevates (from 0.08 to 3.21 ml mg⁻¹ cm⁻¹). This causes a large absorbance at the laser line, resulting in the pronounced ROS content. The collaborative impact of NCP under laser exposure is also investigated through drug release assessment according to photo-bio-modulation (PBM), compared to the absence of laser irradiation. Laser stimulation gives rise to the prompt drug release within a cancerous pH environment of 6.9 (87 % during 40 min), attesting to the synergistic effect of coherent light on NCP. Hence, the systematic measurements reveal that NCP is a ROS-responsive composite for satisfactory drug delivery. The results further validate the cytotoxic effects of the NCP combined with laser treatment on C6 glioma cells, as demonstrated by the MTT assay. This innovative approach holds promise for improving therapeutic outcomes in glioblastoma treatment.