Enhancing photodynamic therapy via encapsulated temoporfin by silica nanoparticles: A red blood cell–based efficacy and modeling study

Photodynamic Therapy (PDT) is an effective treatment in select cancers.. Unfortunately, in clinical practice, PDT may be hindered by poor delivery and stability of the photosensitizers, which are essential for conducting PDT, as well as by significant side effects and aggregation. The aim of this study was to incorporate the second-generation chlorin-based photosensitizer, Temoporfin, into silica nanoparticles (SiNPs) to improve the safety and efficacy of PDT. Due to their ability to control the delivery of oxygen to the tumor microenvironment, red blood cells (RBCs) were chosen as biological targets. Selective photodynamic damage to red blood cells may influence oxygen transport dynamics in the local microenvironment, suggesting a potential mechanism that could be relevant to tumor-associated hypoxia in future therapeutic models. Temoporfin was microemulsified, encapsulated within silica nanoparticles, and characterized for size, shape, and stability. Multiple photodynamic experiments were conducted with varying concentrations and exposure times to compare free Temoporfin and the encapsulated formulation. The formulation encapsulated in silica nanoparticles demonstrated photodynamic effects at much lower doses and shorter exposure times compared to the free formulation, largely due to improved light absorption, enhanced reactive oxygen species generation, and reduced aggregation of the photosensitizer within the silica polymer. The observations of this study provide a detailed reference for the design and fabrication of efficient photodynamic therapy systems, and the silica nanoparticles are encouraged to be used for sustained photosensitizer delivery. In addition, mathematical models were developed to relate the concentration of the drug to the time required to induce 50 % RBC death (t₅₀) for both free and encapsulated Temoporfin. These models provide an initial estimate for refining PDT treatment parameters and can help limit extensive experimental optimization. Overall, the study underscores the efficacy of silica nanoparticles as drug carrier systems for photosensitizers and supports their use in developing more refined, efficient, and biocompatible PDT approaches. This approach can be particularly useful for future cancer treatment models and can be extended to other areas of biomedicine.