Cell-specific and pH-sensitive nanostructure hydrogel based on chitosan as a photosensitizer carrier for selective photodynamic therapy

The major problems of porphyrins as promising materials for photodynamic therapy (PDT) are their low solubility, subsequently aggregation in biological environments, and a lack of tumor selectivity. With this in mind, a chitosan-based hydrogel conjugated with tetrakis(4-aminophenyl)porphyrin (NH2-TPP) and 2,4,6-tris(p-formylphenoxy)-1,3,5-triazine (TRIPOD) via Schiff base linkage, functionalized with folate was designed and synthesized as a pH-sensitive, self-healable and injectable targeted PS delivery system. This new hydrogel was characterized by FT-IR, 1H NMR, SEM, UV-vis, fluorescence spectroscopy and zeta potential. Formation of imine bonds with the aldehyde group of TRIPOD and amine group of NH2-TPP and chitosan, as a dynamic connection, was approved by rheological analysis. Spectroscopic characterizations revealed that aggregation of porphyrin in aqueous media was eliminated due to diminished π stacking interaction of porphyrin in 3D cross-linked hydrogel structure. Hydrogel 3D microporous structure efficiently transfers the excitation energy to the porphyrin unit, yielding improvement singlet oxygen releases. Cytotoxicity and phototoxicity analysis of the CS/NH2-TPP/FA hydrogels indicating an excellent capability to kill cancer cells selectively and prevent damage to normal cells. This work presents a new and efficient model for the preparation of highly efficient and targeting photosensitizer delivery system.