RESUMEN
Here, we report the fabrication of an antioxidant photosensitizing hydrogel system based on chitosan (CS-Cy/PBI-DOPA) covalently cross-linked with perylene bisimide dopamine (PBI-DOPA) as a photosensitizer. The severe insolubility and low tumor selectivity limitations of perylene were overcome by conjugation with dopamine and then to the chitosan hydrogel. The mechanical and rheological study of CS-Cy/PBI-DOPA photodynamic antioxidant hydrogels illustrated interconnected microporous morphologies with high elasticity, swelling ability, and suitable shear-thinning behavior. Bio-friendly properties, such as biodegradability and biocompatibility, excellent singlet oxygen production abilities, and antioxidant properties were also delivered. The antioxidant effects of the hydrogels control the physiological levels of reactive oxygen species (ROS) generated by photochemical reactions in photodynamic therapy (PDT), which are responsible for oxidative damage to tumor cells while protecting normal cells and tissues from ROS damage, including blood and endothelial cells. In vitro, PDT tests of hydrogels were conducted on two human breast cancer cell lines, MDA-MB-231 and MCF-7. These hydrogels offered more than 90% cell viability in the dark and good photocytotoxicity performance with 53 and 43% cell death for MCF-7 and MDA-MB-231 cells, which confirmed their promising potential for cancer therapeutic applications.
Asunto(s)
Neoplasias de la Mama , Quitosano , Perileno , Fotoquimioterapia , Humanos , Femenino , Quitosano/química , Hidrogeles/farmacología , Hidrogeles/química , Antioxidantes/farmacología , Perileno/farmacología , Dopamina , Neoplasias de la Mama/tratamiento farmacológico , Células Endoteliales , Especies Reactivas de Oxígeno , DihidroxifenilalaninaRESUMEN
Tris(2-(2-formylphenoxy)ethyl)amine was designed and synthesized by reaction of salicylaldehyde with tris(2-chloroethyl)amine hydrochloride and evaluated as a new multi-functional cross-linker for preparation of new pH- and thermo-responsive chitosan hydrogels through formation of covalent Schiff-base linkage. The structure and properties of the hydrogels were characterized by FT-IR, 1H NMR and scanning electron microscopy (SEM). The swelling behavior of prepared hydrogels at different pHs and temperatures was investigated. Also, in vitro controlled release behavior of the metronidazole model drug was studied with prepared hydrogels. The release profiles of metronidazole from the hydrogels were determined by UV-Vis absorption measurement. The results showed that the new hydrogels exhibit a pH and temperature-responsive swelling ratio. Also, the pH and temperature were found to strongly influence the drug release behavior of these swollen polymers. Due to the concurrent rapid and significant stimuli-response, these smart hydrogels prepared from chitosan as a natural polymer may expand the scope of hydrogel applications in various fields of research such as targeted (cellular or tissue) delivery of drugs. In addition, these new hydrogels can be used to improve bioavailability, sustain release of drugs or solubilize drugs for systemic delivery.