Biofilm microenvironment triggered self-enhancing photodynamic immunomodulatory microneedle for diabetic wound therapy

Li Yang, Dan Zhang, Wenjing Li, Hongbing Lin, Chendi Ding, Qingyun Liu, Liangliang Wang, Zimu Li, Lin Mei, Hongzhong Chen (), Yanli Zhao () and Xiaowei Zeng ()
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Li Yang: Sun Yat-sen University
Dan Zhang: Sun Yat-sen University
Wenjing Li: Sun Yat-sen University
Hongbing Lin: Sun Yat-sen University
Chendi Ding: Chinese Academy of Medical Sciences & Peking Union Medical College
Qingyun Liu: Sun Yat-sen University
Liangliang Wang: Sun Yat-sen University
Zimu Li: Sun Yat-sen University
Lin Mei: Sun Yat-sen University
Hongzhong Chen: Sun Yat-sen University
Yanli Zhao: Nanyang Technological University
Xiaowei Zeng: Sun Yat-sen University

Nature Communications, 2023, vol. 14, issue 1, 1-17

Abstract: Abstract The treatment of diabetic wounds faces enormous challenges due to complex wound environments, such as infected biofilms, excessive inflammation, and impaired angiogenesis. The critical role of the microenvironment in the chronic diabetic wounds has not been addressed for therapeutic development. Herein, we develop a microneedle (MN) bandage functionalized with dopamine-coated hybrid nanoparticles containing selenium and chlorin e6 (SeC@PA), which is capable of the dual-directional regulation of reactive species (RS) generation, including reactive oxygen species (ROS) and reactive nitrogen species (RNS), in response to the wound microenvironment. The SeC@PA MN bandage can disrupt barriers in wound coverings for efficient SeC@PA delivery. SeC@PA not only depletes endogenous glutathione (GSH) to enhance the anti-biofilm effect of RS, but also degrades GSH in biofilms through cascade reactions to generate more lethal RS for biofilm eradication. SeC@PA acts as an RS scavenger in wound beds with low GSH levels, exerting an anti-inflammatory effect. SeC@PA also promotes the M2-phenotype polarization of macrophages, accelerating wound healing. This self-enhanced, catabolic and dynamic therapy, activated by the wound microenvironment, provides an approach for treating chronic wounds.

Date: 2023
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DOI: 10.1038/s41467-023-43067-8

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