Albumin/Magnetite/Hematoporphyrin Composite Nanoparticles as Drug Carriers for the Photodynamic Therapy of Oral Squamous Cell Carcinoma

Hematoporphyrin, a photosensitizer, has substantial potential for photodynamic therapy (PDT) in oral squamous cell carcinoma (OSCC). However, the strong hydrophobic interactions between hematoporphyrin molecules cause them to easily aggregate, leading to poor solubility in water and suppression of active photoreactive sites. To address these challenges, a biomimetic synthesis strategy was employed to organically integrate ferroferric oxide (Fe 3 O 4 ) nanoparticles with hematoporphyrin, resulting in the construction of highly hydrophilic and efficient Fe 3 O 4 /Haematoporphyrin@BSA (BMH) nanoparticles. This delivery system effectively improved the solubility, bioavailability, and PDT efficiency of hematoporphyrin. Compared with free hematoporphyrin, the BMH nanoparticles exhibited a smaller average hydrated particle size with excellent dispersion in the PBS solution. Additionally, BMH nanoparticles demonstrated efficient cellular uptake by CAL27 tumor cells in a shorter time frame. PDT experiments on CAL27 tumor cells revealed that under the same light exposure, the BMH nanoparticles resulted in a 58% increase in ROS generation, leading to a 57% increase in cell death compared to the hematoporphyrin group. Notably, the electron spin resonance spectrometer (ESR) results and structural analysis of the protein cages suggested that the organic integration of Fe 3 O 4 nanoparticles with hematoporphyrin enhanced electron transfer and increased free radical production, thereby improving overall PDT efficiency. This study demonstrated that highly biocompatible BMH protein-cage nanoparticles significantly enhanced the therapeutic potential of hematoporphyrin for PDT in OSCC.