ROS-Responsive Hydrogel Delivering Bio-Nanoselenium for Targeted Therapy of UVB-Induced Skin Photodamage.

用于靶向治疗 UVB 诱导皮肤光损伤的 ROS 响应型水凝胶递送生物纳米硒

Kongdi Zhu, Jiamin Zhao, Tong Li, Shidi Zhang, Chuanming Liu, Zijian Xu, Cong Lv, Guijie Zhang, Yunlu Kang, Jiaqiang Huang (2026) ROS-Responsive Hydrogel Delivering Bio-Nanoselenium for Targeted Therapy of UVB-Induced Skin Photodamage. ACS Appl Mater Interfaces (IF: 8.2) 2 区

Abstract

Ultraviolet B (UVB) radiation is a major environmental factor that induces skin photodamage through oxidative stress and inflammation. To address this, we developed a reactive oxygen species (ROS)-responsive hydrogel, SeNPs@HPTA, for the intelligent delivery of biogenic selenium nanoparticles (BioSeNPs) synthesized by Bifidobacterium animalis. The hydrogel was fabricated by cross-linking phenylboronic acid-grafted hyaluronic acid (HA-PBA) with tannic acid (TA), forming dynamic boronic ester bonds that cleave under high ROS conditions to enable on-demand BioSeNPs release. Transcriptomic analysis revealed that B. lactis H15 efficiently reduces selenite (Se(IV)) to elemental SeNPs by upregulating ion transport and NADPH-regenerating pathways. In vitro, SeNPs@HPTA enhanced HaCaT cell viability, scavenged ROS, and promoted cell migration post-UVB irradiation. In vivo, topical application alleviated skin lesions, improved hydration, reduced epidermal hyperplasia, and suppressed collagen degradation. Mechanistically, the hydrogel conferred therapeutic effects by enhancing antioxidant defenses, inhibiting inflammation and attenuating ferroptosis via GPx4/Nrf2 activation. Critically, genetic knockdown of GPx4 abolished its therapeutic effects, establishing a strict dependence on this key selenoenzyme. The formulation exhibited an excellent biosafety profile. This study presents a microbiome-inspired, stimulus-responsive strategy for precise skin photodamage treatment. We anticipate this microbiome-inspired, intelligent delivery system will offer a powerful and precise strategy for treating oxidative stress-related dermatoses.

紫外线B (UVB) 辐射是导致皮肤光损伤的主要环境因素之一，它通过氧化应激和炎症反应诱导皮肤损伤。为了解决这一问题，我们开发了一种活性氧 (ROS) 响应型水凝胶 SeNPs@HPTA，用于智能递送由动物双歧杆菌合成的生物源硒纳米颗粒 (BioSeNPs)。该水凝胶通过将苯硼酸接枝的透明质酸 (HA-PBA) 与单宁酸 (TA) 交联而制备，形成动态硼酸酯键，这些键在高 ROS 条件下断裂，从而实现 BioSeNPs 的按需释放。转录组分析表明，乳双歧杆菌 H15 通过上调离子转运和 NADPH 再生途径，有效地将亚硒酸盐 (Se(IV)) 还原为单质硒纳米颗粒 (SeNPs)。体外实验表明，SeNPs@HPTA 可增强 HaCaT 细胞的活力，清除 ROS，并促进 UVB 照射后的细胞迁移。体内实验表明，局部应用该水凝胶可减轻皮肤损伤，改善皮肤水分，减少表皮增生，并抑制胶原蛋白降解。机制上，该水凝胶通过激活GPx4/Nrf2，增强抗氧化防御能力，抑制炎症反应，并减轻铁死亡，从而发挥治疗作用。值得注意的是，GPx4基因敲除可消除其治疗效果，表明该水凝胶的疗效高度依赖于这种关键的硒酶。该制剂展现出优异的生物安全性。本研究提出了一种受微生物组启发、刺激响应的精准皮肤光损伤治疗策略。我们预期这种受微生物组启发的智能递送系统将为治疗氧化应激相关皮肤病提供一种强效且精准的策略。

Links

http://www.ncbi.nlm.nih.gov/pubmed/41983715
http://dx.doi.org/10.1021/acsami.6c00317

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