Development of Folic Acid-Conjugated and Methylene Blue-Adsorbed Au@TNA Nanoparticles for Enhanced Photodynamic Therapy of Bladder Cancer Cells

Photodynamic therapy (PDT) is a promising treatment for malignancy. However, the low molecular solubility of photosensitizers (PSs) with a low accumulation at borderline malignant potential lesions results in the tardy and ineffective management of recurrent urothelial carcinoma. Herein, we used tannic acid (TNA), a green precursor, to reduce HAuCl4 in order to generate Au@TNA core-shell nanoparticles. The photosensitizer methylene blue (MB) was subsequently adsorbed onto the surface of the Au@TNA nanoparticles, leading to the incorporation of a PS within the organic shell of the Au nanoparticle nanosupport, denoted as Au@TNA@MB nanoparticles (NPs). By modifying the surface of the Au@TNA@MB NPs with the ligand folate acid (FA) using NH2-PEG-NH2 as a linker, we demonstrated that the targeted delivery strategy achieved a high accumulation of PSs in cancer cells. The cell viability of T24 cells decreased to 87.1%, 57.1%, and 26.6% upon treatment with 10 ppm[Au] Au@TNA/MB NPs after 45 min, 2 h, and 4 h of incubation, respectively. We also applied the same targeted PDT treatment to normal urothelial SV-HUC-1 cells and observed minor phototoxicity, indicating that this safe photomedicine shows promise for applications aiming to achieve the local depletion of cancer sites without side effects.