Synthesis and Characterization of Temperature-Sensitive and Chemically Cross-Linked Poly( N-isopropylacrylamide)/Photosensitizer Hydrogels for Applications in Photodynamic Therapy
Citation:
Belali Simin, Savoie Huguette, O'Brien Jessica M, Cafolla Atillio A, O'Connell Barry, Karimi Ali Reza, Boyle Ross W, Senge Mathias O, Synthesis and Characterization of Temperature-Sensitive and Chemically Cross-Linked Poly( N-isopropylacrylamide)/Photosensitizer Hydrogels for Applications in Photodynamic Therapy, Biomacromolecules, 19, 5, 2018, 1592 - 1601Download Item:
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, 1H 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.
Sponsor
Grant Number
Science Foundation Ireland (SFI)
IvP 13/IA/1894
Author's Homepage:
http://people.tcd.ie/sengemDescription:
PUBLISHED
Author: Senge, Mathias
Other Titles:
BiomacromoleculesType of material:
Journal ArticleCollections
Series/Report no:
Biomacromolecules19
5
Availability:
Full text availableKeywords:
Protoporphyrin IX, Hydrogels, Photodynamic therapy, Poly(N-isopropylacrylamide), Photosensitizer, Pheophorbide aDOI:
http://dx.doi.org/10.1021/acs.biomac.8b00293ISSN:
1525-7797Other Identifiers:
29596749Metadata
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