1)海南大学生物医学工程学院,数字医学工程全国重点实验室,海口 570228;2.3)海南大学全健康协同创新中心,海南省生物医学工程重点实验室,海口 570228;3.4)Viral Oncogenesis Group, The Pirbright Institute, Pirbright, Guildford GU24 0NF, UK;4.2)海南大学药学院,热带生物资源教育部重点实验室,新药筛选及评价海南省工程研究中心,海口 570228
These authors contributed equally to this work.
海南省高等学校教育教学改革研究项目(Hnjg2026-25),海南省南海育才项目南海创新人才计划(教育领域)(2025NHYC403),海南省重点研发项目(ZDYF2025SHFZ026,ZDYF2023SHFZ142)和国家自然科学基金(52073077,22065011)。
1)State Key Laboratory of Digital Medical Engineering, School of Biomedical Engineering, Hainan University, Haikou 570228, China;2.3)Key Laboratory of Biomedical Engineering of Hainan Province, Collaborative Innovation Center of One Health, Hainan University, Haikou 570228, China;3.4)Viral Oncogenesis Group, The Pirbright Institute, Pirbright, Guildford GU24 0NF, UK;4.2)Hainan Engineering Research Center for Drug Screening and Evaluation, Key Laboratory of Tropical Biological Resources of Ministry of Education, School of Pharmaceutical Sciences, Hainan University, Haikou 570228, China
This work was supported by grants from the Higher Education Institution Education and Teaching Reform Research Project of Hainan Province (Hnjg2026-25), the Nanhai Innovation Talent Program (Education Sector) of Hainan Province (2025NHYC403), the Hainan Province Science and Technology Special Fund (ZDYF2025SHFZ026, ZDYF2023SHFZ142), and The National Natural Science Foundation of China (52073077, 22065011).
慢性糖尿病伤口并发多药耐药(MDR)细菌感染对全球健康构成重大挑战,通常导致持续炎症、生物膜形成和血管生成受损。由于细菌进化和不良的伤口环境,传统抗生素越来越无效。利用一氧化氮(NO)、一氧化碳(CO)、硫化氢(H2S)和氢气(H2)等信号分子的气体疗法是一种很有前途的替代方案。这些气体可以穿透细胞外聚合物基质,破坏细菌代谢,促进巨噬细胞极化和新生血管。然而,它们的临床应用受到半衰期短、溶解度低和脱靶毒性的限制。气体释放微/纳米平台的最新进展主要是通过控制释放机制来克服这些挑战。这些平台可以根据特定的刺激释放气体,如高血糖、酸性pH值,或物理触发,如光和超声波。智能递送系统的发展是改善耐多药感染治疗和组织修复治疗效果的关键。尽管取得了进展,但挑战依然存在,包括生物安全问题、可扩展性和监管障碍。未来应致力于精准监测和个性化治疗,结合可穿戴传感技术和人工智能进行自适应给药,推进气体释放平台在复杂糖尿病伤口治疗中的临床应用。
Chronic diabetic wounds, severely complicated by multidrug-resistant (MDR) bacterial infections, represent a profound and escalating global health crisis. The intrinsically hostile microenvironment of diabetic wounds, characterized by localized hypoxia, persistent oxidative stress, and poor vascularization, creates an ideal niche for opportunistic pathogens such as Staphylococcus aureus and Pseudomonas aeruginosa. These bacteria readily construct dense extracellular polymeric substance (EPS) biofilms, which not only physically shield the microbes from host immune responses but also actively trap the wound in a state of chronic, unresolved inflammation. Consequently, conventional systemic and topical antibiotic therapies are becoming increasingly futile, as poor perfusion at the wound site restricts drug bioavailability, while the rapid genetic evolution of bacteria and the impenetrable nature of biofilms lead to catastrophic treatment failures, often culminating in severe tissue necrosis and lower-extremity amputations. To circumvent the limitations of traditional antimicrobials, therapeutic gas delivery has emerged as a highly promising, paradigm-shifting strategy. Gaseous signaling molecules, particularly nitric oxide (NO), carbon monoxide (CO), hydrogen sulfide (H2S), and hydrogen (H2), possess unique physicochemical properties that allow them to seamlessly penetrate dense biofilm matrices and cellular membranes. Once inside, these gases operate via multi-targeted mechanisms that are incredibly difficult for bacteria to develop resistance against; for instance, NO induces severe lipid peroxidation and DNA cleavage in bacteria, CO downregulates pro-inflammatory cytokines, H2S significantly accelerates endothelial cell migration for neovascularization, and H2 acts as a powerful selective antioxidant to neutralize tissue-damaging reactive oxygen species (ROS). Together, these therapeutic gases not only exert broad-spectrum bactericidal effects but also actively reprogram the wound bed by promoting the critical M1-to-M2 macrophage polarization and stimulating angiogenesis. Despite their immense biological potential, the direct clinical translation of gas therapies is severely hindered by inherent physicochemical drawbacks, including extreme volatility, short physiological half-lives, poor aqueous solubility, and the high risk of off-target systemic toxicity, if applied indiscriminately. To conquer these immense pharmacokinetic barriers, cutting-edge advancements in materials science have driven the development of gas-releasing micro- and nanoplatforms. Utilizing sophisticated carriers such as metal-organic frameworks (MOFs), mesoporous silica, polymeric nanoparticles, liposomes, and injectable hydrogels, researchers can now encapsulate gas-donor molecules to achieve sustained, localized delivery. More importantly, these advanced nanoplatforms are ingeniously engineered to be stimuli-responsive. By exploiting the pathological hallmarks of the diabetic wound environment, such as elevated glucose concentrations, acidic pH, and overexpressed ROS, or by utilizing external triggers like near-infrared (NIR) light irradiation and ultrasound, these intelligent platforms ensure on-demand, precise spatio-temporal gas release. This often allows for powerful synergistic combinations, such as photothermal or photodynamic therapy coupled with gas release, thereby obliterating biofilms while sparing healthy tissue. While the therapeutic outcomes of these smart delivery systems in eradicating MDR infections and accelerating tissue repair are unprecedented, several critical challenges remain before widespread clinical adoption, as long-term biosafety profiles of the carrier nanomaterials, complexities in large-scale good manufacturing practice (GMP) production, and stringent regulatory hurdles must be rigorously addressed. Looking forward, the next frontier lies in the realm of precision medicine and theranostics, where future research must focus on the seamless integration of these gas-releasing platforms with flexible, wearable biosensors capable of continuously monitoring wound biomarkers (e.g., pH, temperature, uric acid) in real-time. Coupled with artificial intelligence algorithms to govern automated, closed-loop adaptive dosing, these next-generation smart dressings hold the ultimate potential to comprehensively transform the clinical management of complex, infected diabetic wounds.
刘若灿,王玉倩,张帅,左绍志,吴云娣,吴锡龙.释气微纳米平台用于多重耐药菌感染性糖尿病伤口治疗[J].生物化学与生物物理进展,2026,53(5):1356-1375 LIU Ruo-Can, WANG Yu-Qian, ZHANG Shuai, ZUO Shao-Zhi, WU Yun-Di, WU Xi-Long. Advancements in Gas-releasing Micro/Nanoplatforms for Overcoming MDR Bacterial Infections in Diabetic Wounds[J]. Progress in Biochemistry and Biophysics,2026,53(5):1356-1375
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