Photothermally-activated nano-delivery system for on-demand treatment of diabetic wound infections

Sep 29, 2026

Bacterial-infected diabetic wounds in a persistent hyperglycemic state often suffer impaired healing due to secondary infections and chronic inflammation. The study constructs an NIR light-activated intelligent hydrogel drug delivery system, LSZBP@CMO, combining efficient photothermal components with a pH-responsive CMO hydrogel for dual-stimuli controlled release. NIR induces localized mild hyperthermia, disrupting thermosensitive structures and accelerating drug release under acidic microconditions. In vitro and in vivo results show strong antibacterial activity and improved repair in infected diabetic rats, with a wound healing ratio of 97.39 ± 1.60% by day 7.

LanguageEnglish

CategoryHealthcare

FormatPDF

Pages15

Reading Time38 min

AccessFree to download

Introduction

Hyperglycemia-driven inflammation and impaired diabetic wound healing

Metal nanoparticles and antibacterial mechanisms

Study design: NIR-activated intelligent hydrogel delivery system

Results in vitro and in vivo

Conclusions

International Journal of Pharmaceutics: X 11 (2026) 100464 Contents lists available at ScienceDirect International Journal of Pharmaceutics: X journal [homepage:](homepage: www.sciencedirect.com/journal/international-journal-of-pharmaceutics-x)[ www.sciencedirect.com/journal/international-journal-of-pharmaceutics-x](homepage: www.sciencedirect.com/journal/international-journal-of-pharmaceutics-x) | Photothermally-activated nano-delivery system for on-demand treatment of diabetic wound infections
Rong Huang a, Wenjia Yanga, Tao Wang a, Xianbin Cao a, Shiyu Sun b, Jiaxin Jiang c, Hongsheng Liu c, Jianzhong Penga,*
a Department of Dermatologic Surgery, Hangzhou Third People’s Hospital, Hangzhou, Zhejiang 310000, PR China
b Department of Rehabilitation Medicine, The Affiliated Guangdong Second Provincial General Hospital of Jinan University, Guangzhou, Guangdong 510310, PR China c Guangdong Huayi Biomedical Science and Technology Center, Guangzhou, Guangdong 511450, PR China | | | | --- | --- | --- | | A R T I C L E I N F O | | A B S T R A C T | | Keywords:
Photothermal effect Thermosensitive barrier Bacterial infection Diabetic wound | | Bacterial-infected diabetic wounds, characterized by a persistent hyperglycemic environment, susceptibility to secondary bacterial infections, and chronic inflammatory responses, often exhibit impaired healing processes, posing a significant challenge in clinical management. To address this issue, this study designed and constructed a near-infrared (NIR) light-activated intelligent hydrogel drug delivery system—LSZBP@CMO. This system integrates highly efficient photothermal conversion components with a pH-responsive CMO hydrogel based on Schiff base reactions, achieving a dual-stimuli responsive drug release mechanism governed by exogenous NIR light and endogenous microenvironmental acidity. Under NIR irradiation, localized mild hyperthermia is generated, leading to the disruption of thermosensitive structures within the system and exposure of nanoparticles. This process, synergizing with the mildly acidic environment, further triggers rapid drug release, significantly enhancing antibacterial efficacy. Both in vitro and in vivo experimental results demonstrated that LSZBP@CMO not only efficiently eliminates bacteria but also effectively alleviates oxidative stress, modulates the inflammatory microenvironment, and markedly promotes angiogenesis, collagen deposition, and epithelial regeneration. In a diabetic rat model with infected wounds, the treatment group exhibited outstanding repair performance, achieving a wound healing ratio of 97.39 ± 1.60 % by day 7. This study provides an actively controllable strategy with promising clinical application prospects for on-demand therapy of refractory bacterialinfected diabetic wounds. | 1. Introduction Bacterial infection and excessive inflammation are key factors that impede the healing of diabetic wounds (Wang et al., 2023a; Sun et al., 2024). In a hyperglycemic environment, persistent inflammatory responses disrupt the normal progression of wound repair into the proliferation and remodeling phases (Pan et al., 2025b). The accumulation of advanced glycation end products (AGEs), driven by chronic hyperglycemia, leads to thickening of the microvascular basement membrane and endothelial dysfunction, resulting in inadequate tissue perfusion and hypoxia (Liu et al., 2025b). Furthermore, M1 macrophage polarization dominates the wound site, maintaining the diabetic wound in a prolonged pro-inflammatory state with continuous secretion of inflammatory cytokines (Xia et al., 2025). Abnormal function offibroblasts can also reduce the synthesis of collagen, thereby further hindering the transition from the inflammatory stage to the proliferative stage, and ultimately leading to the formation of chronic non-healing ulcers (Dinget al., 2024). Meanwhile, the hyperglycemic microenvironment promotes colonization by pathogenic bacteria such a

FAQs

What problem does the study address in diabetic wound infections?

Bacterial-infected diabetic wounds are characterized by persistent hyperglycemia, susceptibility to secondary bacterial infections, and chronic inflammatory responses that impair healing and complicate clinical management.

How does LSZBP@CMO achieve on-demand drug release?

LSZBP@CMO integrates NIR-triggered photothermal conversion with a pH-responsive CMO hydrogel, so drug release is governed by exogenous NIR light and endogenous acidic microenvironment.

What outcomes were observed in diabetic rats with infected wounds?

The treatment group showed strong repair performance, including efficient bacterial elimination and improved healing, reaching a wound healing ratio of 97.39 ± 1.60% by day 7.

Sep 29, 2026

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