Design and synthesis of nanoscale titanium-porphyrin coordination nanomaterials for photodynamic-sonodynamic synergistic therapy of tumor cells

Aim: Multifunctional nanomaterials with photodynamic-sonodynamic therapy (PSDT) potential offer significant advantages in cancer treatment. However, designing and preparing single-component “two-in-one” multifunctional nanomaterials remains challenging. Hematoporphyrin monomethyl ether (HMME), a second-generation porphyrin-related sonosensitizer, is a porphyrin derivative with two asymmetric carboxyl groups. Notably, the carboxyl groups in HMME can coordinate with metal ions to construct metal-organic coordination nanomaterials (MCPs). Titanium (Ti), a biocompatible metal element, is commonly used in medical devices such as implantable metal alloys. Therefore, this study reported the synthesis of “two-in-one” type Ti-HMME coordination nanomaterials (TiCPs) as efficient nanoscale photo/sonosensitizers. Methods: Under a nitrogen atmosphere, TiCPs were synthesized via self-assembly between HMME and Ti4+ ions. Results: The average particle size of TiCPs was approximately 70 nm. Additionally, TiCPs contained the photo/sonosensitizer HMME, which could convert O2 into cytotoxic reactive oxygen species (ROS) under light and ultrasound (US) excitation. The generation of ROS could be detected using 1,3-diphenylisobenzofuran (DPBF). When the mixed solution (TiCPs + DPBF) was irradiated with light, the DPBF peak rapidly decreased with increasing irradiation time, indicating the production of ROS by TiCPs under light. Similarly, the absorbance of TiCPs + DPBF significantly decreased with increasing US time, demonstrating the sonodynamic effect of TiCPs + US. After 10 min of light or US excitation, 49.4% (Light) and 38.1% (US) of DPBF were oxidized by ROS generated by TiCPs, showcasing excellent photodynamic/sonodynamic effects. In vitro cell experiments further demonstrated that TiCPs had excellent biocompatibility, could be effectively internalized by cells, and significantly reduced cell viability under light and US excitation, effectively killing tumor cells. Conclusions: This study not only demonstrated TiCPs as “two-in-one” type multifunctional nanomaterials for PSDT but also provided insights into designing other photo/sonosensitizer molecules with similar HMME structures for tumor theranostics.