NIR photo-responsive injectable chitosan/hyaluronic acid hydrogels with controlled NO release for the treatment of MRSA infections

Jan 26, 2025International journal of biological macromolecules

Injectable gels that release nitric oxide when activated by near-infrared light to treat MRSA infections

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Regenerative Health on OpenScience ↗PubMed ↗DOI ↗

Abstract

The CHDTA hydrogel demonstrates bactericidal rates of 99.4% against Staphylococcus aureus and 98.8% against methicillin-resistant Staphylococcus aureus (MRSA).

The hydrogel is formed by crosslinking carboxymethyl chitosan with hyaluronic acid.
Incorporation of polydopamine, a photosensitizer, and L-arginine as a nitric oxide donor enhances its therapeutic properties.
The hydrogel exhibits both photodynamic therapy and photothermal therapy effects under specific near-infrared light irradiation.
L-arginine reacts with singlet oxygen produced during photodynamic therapy to generate nitric oxide, contributing to its antibacterial action.
In vivo studies indicate the hydrogel promotes wound healing in MRSA-infected animal models.

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Due to resistance to common antibiotics, methicillin-resistant Staphylococcus aureus (MRSA) infections pose a significant threat to human health. In this study, we developed an injectable, adhesive, and biocompatible hydrogel with multiple functions. Specifically, carboxymethyl chitosan (CMCS) crosslinked with hyaluronic acid (HA) forms the primary framework of the hydrogel. Subsequently, polydopamine (PDA), 5,10,15,20-tetrakis (4-aminophenyl) porphyrin (TAPP), and L-arginine (L-Arg) are incorporated as a photothermal agent, photosensitizer, and nitric oxide (NO) donor, respectively, resulting in the CHDTA hydrogel. Under the combined irradiation of 660 nm and 808 nm near-infrared (NIR) light, the CHDTA hydrogel exhibits both photodynamic therapy (PDT) and photothermal therapy (PTT) effects. Simultaneously, L-Arg reacts with singlet oxygen (O), generated via the PDT effect, leading to the production of NO. The CHDTA hydrogel effectively inhibits the activity of Staphylococcus aureus (S. aureus) and MRSA, achieving bactericidal rates of 99.4 % and 98.8 %, respectively, through a combination of PDT, PTT, and NO synergistic antibacterial mechanisms. In vivo studies demonstrate the excellent antibacterial properties and wound healing promotion of the CHDTA hydrogel in MRSA-infected animal wound models. The hydrogel system developed in this study integrates multiple functional design concepts and serves as a potential therapeutic platform for combating MRSA infections. 1 2

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NIR photo-responsive injectable chitosan/hyaluronic acid hydrogels with controlled NO release for the treatment of MRSA infections

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