Preprint Article Version 1 Preserved in Portico This version is not peer-reviewed

Facile Fabrication of NIR-Responsive Alginate/CMC Hydrogels Derived through IEDDA Click Chemistry for Photothermal-Photodynamic Anti-tumor Therapy

Version 1 : Received: 22 November 2023 / Approved: 22 November 2023 / Online: 22 November 2023 (08:52:40 CET)

A peer-reviewed article of this Preprint also exists.

Rizwan, A.; Ali, I.; Jo, S.-H.; Vu, T.T.; Gal, Y.-S.; Kim, Y.H.; Park, S.-H.; Lim, K.T. Facile Fabrication of NIR-Responsive Alginate/CMC Hydrogels Derived through IEDDA Click Chemistry for Photothermal–Photodynamic Anti-Tumor Therapy. Gels 2023, 9, 961. Rizwan, A.; Ali, I.; Jo, S.-H.; Vu, T.T.; Gal, Y.-S.; Kim, Y.H.; Park, S.-H.; Lim, K.T. Facile Fabrication of NIR-Responsive Alginate/CMC Hydrogels Derived through IEDDA Click Chemistry for Photothermal–Photodynamic Anti-Tumor Therapy. Gels 2023, 9, 961.

Abstract

A novel chemically cross-linked hydrogel was prepared through the utilization of the nor-bornene (Nb)-methyl tetrazine (mTz) click reaction, derived from carboxymethyl cellulose (CMC) and alginate (Alg). The hydrogel was designed to generate reactive oxygen species (ROS) from NIR-dye, indocyanine green (ICG) for a combined photothermal and photodynamic ther-apy (PTT/PDT). The cross-linking of Nb and mTz moieties occurred via an inverse elec-tron-demand Diels-Alder reaction under physiological conditions avoiding the need for a cata-lyst. The resulting hydrogels exhibited viscoelastic properties (G′ ~ 492-270 Pa) and high porosi-ty. The hydrogels were found to be injectable with tunable mechanical characteristics. The ICG encapsulated hydrogels demonstrated ROS generation ability under NIR exposure. The ROS production was investigated through DPBF assays to access photodynamic effect (with NIR irra-diation at 1-2W for 5-15 min). The temperature of the ICG-loaded hydrogels was also raised up-on the NIR irradiation to eradicate tumor cells photothermally. In vitro cytocompatibility as-sessments revealed the non-toxic nature of CMC-Nb and Alg-mTz towards HEK-293 cells. Fur-thermore, the ICG-loaded hydrogels effectively inhibited the metabolic activity of Hela cells following NIR exposure. This innovative hydrogel system holds promise for applications in combined PTT and PDT.

Keywords

carboxymethyl cellulose-norbornene; alginate-methyl tetrazine; indocyanine green; NIR-responsive hydrogels

Subject

Chemistry and Materials Science, Biomaterials

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