Synthesis and Characterization of Temperature-Sensitive and Chemically Cross-Linked Poly(N-isopropylacrylamide)/Photosensitizer Hydrogels for Applications in Photodynamic Therapy

Abstract

A novel poly( N-isopropylacrylamide) (PNIPAM) hydrogel containing different photosensitizers (protoporphyrin IX (PpIX), pheophorbide a (Pba), and protoporphyrin IX dimethyl ester (PpIX-DME)) has been synthesized with a significant improvement in water solubility and potential for PDT applications compared to the individual photosensitizers (PSs). Conjugation of PpIX, Pba, and PpIX-DME to the poly( N-isopropylacrylamide) chain was achieved using the dispersion polymerization method. This study describes how the use of nanohydrogel structures to deliver a photosensitizer with low water solubility and high aggregation tendencies in polar solvents overcomes these limitations. FT-IR spectroscopy, UV-vis spectroscopy, H NMR, fluorescence spectroscopy, SEM, and DLS analysis were used to characterize the PNIPAM-photosensitizer nanohydrogels. Spectroscopic studies indicate that the PpIX, Pba, and PpIX-DME photosensitizers are covalently conjugated to the polymer chains, which prevents aggregation and thus allows significant singlet oxygen production upon illumination. Likewise, the lower critical solution temperature was raised to ∼44 °C in the new PNIPAM-PS hydrogels. The PNIPAM hydrogels are biocompatible with>90% cell viability even at high concentrations of the photosensitizer in vitro. Furthermore, a very sharp onset of light-dependent toxicity for the PpIX-based nanohydrogel in the nanomolar range and a more modest, but significant, photocytotoxic response for Pba-PNIPAM and PpIX-DME-PNIPAM nanohydrogels suggest that the new hydrogels have potential for applications in photodynamic therapy.

Core–shell polymeric nanoparticles co-loaded with photosensitizer and organic dye for photodynamic therapy guided by fluorescence imaging in near and short-wave infrared spectral regions

“…Value of T 0 can be shifted to 34-42 °C by copolymerization of NIPAM with more hydrophilic monomers, e.g. acrylamide (AA) [30]. In the developed NPs, shell is of poly(NIPAM-co-AA) copolymer, which makes NPs thermoresponsive.…”

Hydrogels: soft matters in photomedicine

“…Moreover, incorporation into hydrogels did not affect the efficiency of ROS production, which makes them promising candidates as drug delivery platforms for PS. 185 Furthermore, Zampini et al studied hydrogels with incorporated silica-PPIX samples in the presence of gold nanoparticles. This preliminary study showed enhanced ROS production and an improved excitation field due to plasmonic effect.…”

“…This indicated uptake by the cells via folate-receptor Pheo a was also covalently linked to the hydrogel matrix of PNIPAM to yield a stable and water soluble nanohydrogel formulation. 185 This nanoporous 3D structure prevented the aggregation of the PS and enhanced the efficiency of singlet oxygen production. The photosensitizer also displayed an excellent in vitro PDT efficacy wherein Pheo a-PNIPAM formulation gave a LD 90 of 9 × 10 -5 as compared to Pheo a alone, which displayed a LD 90 of 5 × 10 -7 (HT-29 cancer cells).…”

Anti‐Sandwich Structured Photo‐Electronic Wound Dressing for Highly Efficient Bacterial Infection Therapy

“…[ 18 ] Light‐irradiation responsive hydrogels also showed great PDT success. [ 19 ] Our group developed a new cationic chalcogenoviologens‐loaded WD, which exhibited a significant photodynamic antibacterial effect and the ability to promote skin regeneration. [ 20 ] However, such WD cannot provide convenient treatment under electrical stimulation at the same time.…”