Protoporphyrin IX–Chitosan Oligosaccharide Conjugate with Potent Antifungal Photodynamic Activity

A new chemical conjugate between protoporphyrin IX (PPIX) and chitosan oligosaccharides (CH) was prepared and evaluated in vitro as an antifungal agent against Penicillium digitatum. Chemical characterization and photophysical/photochemical studies were conducted. The antifungal effect of the CH-PPIX conjugate was compared to its components (PPIX and CH) and a physical mixture of both, under dark and illuminated conditions. The CH-PPIX conjugate was photostable and inhibited fungal growth with 100% efficiency at a dose of 0.005% w/v under visible light irradiation, while no antifungal activity was observed in the dark. Under the same conditions, CH and PPIX did not display any fungicidal activity, demonstrating the improved properties of the conjugate. Insights into the mechanism of fungal inactivation revealed an efficient spore uptake and photoinduced membrane damage through singlet oxygen generation. This new bioconjugate, which is based on natural components, represents a promising agent for fungicidal formulations based on antimicrobial photodynamic therapy.