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

Belali, Simin; Savoie, Huguette; O’Brien, Jessica M.; Cafolla, Atillio A.; O’Connell, Barry; Karimi, Ali Reza; Boyle, Ross W.; Senge, Mathias O.

Abstract

Copyright © 2018 American Chemical Society. 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, 1 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.

Citation

Belali, S., Savoie, H., O’Brien, J. M., Cafolla, A. A., O’Connell, B., Karimi, A. R., …Senge, M. O. (2018). Synthesis and Characterization of Temperature-Sensitive and Chemically Cross-Linked Poly(N-isopropylacrylamide)/Photosensitizer Hydrogels for Applications in Photodynamic Therapy. Biomacromolecules, 19(5), 1592-1601. https://doi.org/10.1021/acs.biomac.8b00293

• Journal Article Type: Article
• Acceptance Date: Mar 30, 2018
• Online Publication Date: Apr 6, 2018
• Publication Date: May 14, 2018
• Deposit Date: Jun 4, 2018
• Publicly Available Date: Apr 7, 2019
• Journal: Biomacromolecules
• Print ISSN: 1525-7797
• Electronic ISSN: 1526-4602
• Publisher: American Chemical Society
• Peer Reviewed: Peer Reviewed
• Volume: 19
• Issue: 5
• Pages: 1592-1601
• DOI: https://doi.org/10.1021/acs.biomac.8b00293
• Keywords: Materials Chemistry; Bioengineering; Polymers and Plastics; Biomaterials
• Public URL: https://hull-repository.worktribe.com/output/816892
• Publisher URL: https://pubs.acs.org/doi/10.1021/acs.biomac.8b00293