Co-Immobilization of Ce6 Sono/Photosensitizer and Protonated Graphitic Carbon Nitride on PCL/Gelation Fibrous Scaffolds for Combined Sono-Photodynamic Cancer Therapy

Aiming at developing a moderate and efficient sonophotodynamic therapy for breast cancer, tissue engineering scaffolds may provide an easy and efficient strategy to eliminate serious side effects in conventional surgery or chemotherapy, and thus, they are highly desired. However, the development of ideal sono-photodynamic therapeutic scaffolds is always hindered by the poor stability and incompatibility between the different biomaterial components. Herein, the Food and Drug Administration (FDA)-approved sono/photosensitizer Chlorin e6 (Ce6) was successfully and tightly incorporated into electrospun polycaprolactone/gelatin (PG) scaffolds via positively charged protonated g-C3N4 nanosheets (pCN). The PG fibers were precoated with graphene oxide (GO) to enable the assembly of pCN on the surface through electrostatic interactions. The Ce6@pCN-GO-PG composite scaffolds exhibited good cytocompatibility and excellent sono-photodynamic activity, leading to distinctly boosted reactive oxygen species (ROS) generation and a 95.8% inactivation rate of breast cancer cells through a synergistic sono-photodynamic process triggered by an 808 nm laser and 1 MHz ultrasound (US) excitation, within the clinical therapeutic dose. The as-developed scaffolds with unique ultrasound cavitation therapeutic effects can be used not only for complete eradication of tumor cells after surgery but also as a cell behavior observation platform of sono-photodynamic cancer therapy.