Novel nanostructured smart, photodynamic hydrogels based on poly(N-isopropylacrylamide) bearing porphyrin units in their crosslink chains: A potential sensitizer system in cancer therapy

Abstract

Novel nanostructure, pH-thermo dual responsive photodynamic hydrogels based on poly(N-isopropylacrylamide) were successfully synthesized by in situ dispersion polymerization of NIPAAm with 5,10, 15, 20-tetrakis(4-N-carbonylacrylic aminophenyl)porphyrin (2% and 4% w/w) in the presence of methylene-bis-acrylamide (MBA) in water. 5, 10, 15, 20-tetrakis (4-N-carbonylacrylic aminophenyl)porphyrin (CAA-TPP) was designed and synthesized for the first time via reaction of tetrakis(4-aminophenyl)porphyrin (NH2-TPP) with maleic anhydrid and was applied as a crosslinker. The structure of the 5, 10, 15, 20-tetrakis(4-N-carbonylacrylic aminophenyl) porphyrin and hydrogels was thoroughly studied by a variety of techniques such as NMR, FT-IR and UV–visible spectrophotometer. The surface morphology of freeze-dried hydrogels using SEM showed one-dimensional nanostructured with uniform morphology of self-assembled interconnected nanofibers. Rheological measurement results were showed that the incorporation of porphyrin onto polymer structure can provide hydrogels without the loss of thermoresponsive viscoelastic properties. The lower critical solution temperatures (LCST) of P[NIPAAm-co-CAA-TPP] hydrogels in water were measured by the cloud point (CP) method. The LCST of P[NIPAAm-co-CAA-TPP (2%)] and P[NIPAAm-co-CAA-TPP (4%)] were at about 40 °C and 43 °C, respectively. The results showed that an increase in porphyrin content makes the LCSTs of the hydrogels increase. Swelling measurements of hydrogels indicated sensitivity to temperature and pH, suggesting that the P[NIPAAm-co-CAA-TPP]s were temperature/pH dual stimulus-responsive hydrogels. In this work, the efficiency of P[NIPAAm-co-CAA-TPP (2%)] and P[NIPAAm-co-CAA-TPP (4%)] as photodynamic therapy (PDT) systems were investigated. The production of reactive singlet oxygen, cytotoxity and phototoxicity of them were assessed. The study showed that the singlet oxygen production ability of P[NIPAAm-co-CAA-TPP (2%)] can be well controlled by irradiation time compared with free porphyrin. We tested these two hydrogels on A453 cells to compare their effectiveness. P[NIPAAm-co-CAA-TPP (2%)] and P[NIPAAm-co-CAA-TPP (4%)] exhibited cell viability over 97% and good photocytotoxity, indicating they are promising photodynamic systems for cancer therapy.