Targeting starvation therapy for diabetic bacterial infections with endogenous enzyme-triggered hyaluronan-modified nanozymes in the infection microenvironment.
Liu. Yijun Y; Zhang. Xuan X; Yang. Silan S; Guo. Qiuyan Q; Zhang. Yuying Y; Wang. Zishu Z; Xu. Shan S; Qiao. Dan D; Ma. MeiGui M; Zheng. Pengwu P; Zhu. Wufu W; Pan. Qingshan Q
Key Findings
- LL‑37 guides the nano‑system to infection sites in diabetic wounds
- Hyaluronidase in the wound breaks the hyaluronic‑acid shell, releasing antibacterial nano‑enzymes
- The metal‑based nano‑enzymes kill bacteria via photothermal and chemodynamic effects and improve wound healing
Practical Outcomes
- This research shows a promising future treatment for diabetic wound infections, but the technology is still experimental and requires complex nanomaterial synthesis. It isn’t something biohackers can apply now, though it highlights the potential of peptide‑targeted, enzyme‑triggered nanotherapies for future DIY or clinical use.
Summary
Scientists made a tiny particle that uses the natural antimicrobial peptide LL‑37 to find infected diabetic wounds, then releases enzyme‑based weapons when the wound’s own hyaluronidase breaks down a coating. The particles also heat up with light to help kill bacteria and speed healing, and they worked well in lab tests and mouse models.
Abstract
The high-glycemic microenvironment of diabetic wounds promotes bacterial proliferation, leading to persistent infections and delayed wound healing. This poses a significant threat to human health, necessitating the development of new nanodrug visualization platforms. In this study, we designed and synthesized cascade nano-systems modified with targeted peptide and hyaluronic acid for diabetic infection therapy. The nano-systems were able to target the site of infection using LL-37, and in the microenvironment of wound infection, the hyaluronic acid shell of the nano-systems was degraded by endogenous hyaluronidase. This precise degradation released a cascade of nano-enzymes on the surface of the bacteria, effectively destroying their cytoskeleton. Additionally, the metals in the nano-enzymes provided a photo-thermal effect, accelerating wound healing. The cascade nano-visualization platform demonstrated excellent bactericidal efficacy in both in vitro antimicrobial assays and in vivo diabetic infection models. In conclusion, this nano-system employs multiple approaches including targeting, enzyme-catalyzed therapy, photothermal therapy, and chemodynamic therapy to kill bacteria and promote healing. The Ag@Pt-Au-LYZ/HA-LL-37 formulation shows great potential for the treatment of diabetic wounds.
Study Information
pubmed
2024
2024-05-10T00:00:00.000Z
10.1016/j.ijbiomac.2024.132277
11
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