| Summary: | Photodynamic therapy (PDT) is a cutting-edge cancer treatment that utilizes both light and photosensitizers (PSs) to attack cancer cells. Methylene blue (MB) has emerged as a highly promising photosensitizer (PS) in PDT therapy due to its exceptional ability to produce singlet oxygen, which is attributed to its high quantum yield. However, the main challenge in utilizing MB in photodynamic therapy is its effective delivery to the target tissue. This challenge can be addressed by utilizing silica nanoparticles (SiNPs) as a drug delivery agent. Silica nanoparticles encapsulate MB and prevent its leakage, offering a novel approach to improving PDT therapy by reducing the toxicity of MB and increasing its bioavailability at the target cell. In this study, an extensive analysis of the size and shape evolution of the synthesized silica nanoparticles loaded with MB was conducted using TEM. Various encapsulated and bare MB concentrations were tested for cytotoxicity against osteosarcoma cells. Moreover, the optimal concentration and exposure time under light (with an intensity of approximately 8.9 mW/cm<sup>2</sup> in the visible range) were determined to achieve maximum cell elimination. The results revealed that encapsulated MB in SiNPs exhibited a higher efficacy compared to naked MB, with a 50% increase in concentration effectiveness and a 90% increase in exposure time efficacy. This confirms that encapsulated MB in SiNPs is more effective in killing osteosarcoma cells than bare MB, thereby enhancing photodynamic therapy through increased bioavailability of MB in target cells. The enhanced bioavailability of MB in target cells as a result of its encapsulation in SiNPs makes it a highly promising drug delivery candidate for significantly enhancing the efficacy of photodynamic therapy against osteosarcomas.
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