Metal-phenolic network crosslinked nanogel with prolonged biofilm retention for dihydroartemisinin/NIR synergistically enhanced chemodynamic therapy.

Chemodynamic therapy (CDT) is emerging as a promising treatment for biofilm infections. However, its effectiveness is significantly hindered by several factors: the body's stable temperature, a limited supply of Fe ²⁺ ions, and inadequate endogenous levels of H ₂ O ₂ at the infection sites. Herin, our study introduces MPN-crosslinked hyaluronic acid (HA) nanogels as an effective strategy for treating biofilm-associated infections. The DHA@HA-TA/Fe (DHTF) nanogel is synthesized through the coordination reaction between Fe ²⁺ ions and tannic acid (TA)-modified HA, with dihydroartemisinin (DHA) encapsulated within the structure. DHTF exhibits pH-/hyaluronidase-responsiveness in the biofilm infection microenvironment, enabling sustained release of DHA as a substitute for H ₂ O ₂ and Fe ²⁺ for CDT. The incorporation of Fe ²⁺ /TA-based MPN and DHA within the nanogels enables photothermal/DHA dually-enhanced CDT, facilitating efficient disruption of biofilm matrices and bacterial eradication through boosting reactive oxygen species production. In vivo studies demonstrate that DHTF exhibit prolonged retention within biofilms. This ensures a sustained release of therapeutic agents and continuous anti-biofilm activity. Eventually, both in vitro and in vivo evaluations consistently confirm the significant anti-biofilm capacity of DHTF. Our findings highlight the potential of DHTF as a promising nanomedicine for biofilm-related infections, offering efficient treatment strategies that could improve clinical management of these challenging conditions.
Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.
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