Wu Feng, Zhang Jin, Ye Jiangtian, Wang Jinwu, Zheng Wenhao, Chen Hua, Dong Xiaoyu, Huang Zu-Sheng, Cai Leyi, Xiang Guangheng
Department of Orthopaedics Surgery, The Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University, NO.109, XueYuan West RoadLuheng District, Wenzhou, 325000, Zhejiang, People's Republic of China.
School of Pharmaceutical Sciences, Wenzhou Medical University, Wenzhou, 325000, Zhejiang, China.
J Nanobiotechnology. 2025 Jul 12;23(1):503. doi: 10.1186/s12951-025-03570-0.
Random flaps are primarily employed in clinical practice for wound repair; however, the ischemic necrosis following surgery remains a significant challenge. To address this issue, we developed high-performance near-infrared (NIR) photothermal agent, 6BQ, to enhance random flaps survival through mild photothermal therapy (MPTT). In this study, we assessed the effects of 6BQ NPs on cell viability, proliferation, migration, and angiogenesis of human umbilical vein endothelial cells (HUVECs) using MPTT in vitro. Techniques such as Cell Counting Kit-8(CCK8), wound scratch assay, Transwell assay, tube formation assay, RT-qPCR, and Western blotting were employed, along with an exploration of the related signaling mechanisms. In animal experiments, we utilized the McFarlane flap model in Sprague-Dawley rats, randomly assigning them to Control, 6BQ NPs, and 6BQ NPs + laser irradiation (6BQ NPs + L) groups. On postoperative day 7, we evaluated flap viability, assessed microcirculatory perfusion with laser Doppler flow imaging, and examined angiogenesis, inflammatory response, oxidative stress, and the activity of the Heat shock protein 90(HSP90)/ Hypoxia-inducible factor 1 alpha (HIF-1α) axis using immunological and molecular biological techniques. Results indicated that under 808 nm laser irradiation (0.5 W/cm, 15 min), 6BQ NPs activated the HSP90/HIF-1α axis through MPTT, promoting angiogenesis by upregulating Vascular endothelial growth factor (VEGF) expression. Concurrently, Superoxide dismutase (SOD) content increased while Malondialdehyde (MDA) content decreased through upregulation of Heme oxygenase-1(HO-1) expression, alleviating oxidative stress, and reduced Interleukin-6 (IL-6) and Tumor necrosis factor alpha (TNF-α) expression inhibited the inflammatory response, thereby significantly improving random flaps survival. In conclusion, this study highlights the potential of 6BQ NPs in improving random flaps survival, offering a novel therapeutic strategy for wound repair.
随意皮瓣主要用于临床伤口修复；然而，术后的缺血性坏死仍然是一个重大挑战。为了解决这个问题，我们开发了高性能近红外（NIR）光热剂6BQ，通过温和光热疗法（MPTT）提高随意皮瓣的存活率。在本研究中，我们在体外使用MPTT评估了6BQ纳米颗粒对人脐静脉内皮细胞（HUVECs）的细胞活力、增殖、迁移和血管生成的影响。采用了细胞计数试剂盒-8（CCK8）、划痕实验、Transwell实验、管腔形成实验、RT-qPCR和蛋白质免疫印迹等技术，并探索了相关信号机制。在动物实验中，我们在Sprague-Dawley大鼠中使用McFarlane皮瓣模型，将它们随机分为对照组、6BQ纳米颗粒组和6BQ纳米颗粒+激光照射（6BQ纳米颗粒+L）组。术后第7天，我们评估了皮瓣活力，用激光多普勒血流成像评估微循环灌注，并使用免疫和分子生物学技术检查血管生成、炎症反应、氧化应激以及热休克蛋白90（HSP90）/缺氧诱导因子1α（HIF-1α）轴的活性。结果表明，在808 nm激光照射（0.5 W/cm²,15分钟）下,6BQ纳米颗粒通过MPTT激活HSP90/HIF-1α轴，通过上调血管内皮生长因子（VEGF）表达促进血管生成。同时,超氧化物歧化酶（SOD）含量增加，丙二醛（MDA）含量通过上调血红素加氧酶-1（HO-1）表达而降低，减轻氧化应激,并且白细胞介素-6（IL-6）和肿瘤坏死因子α（TNF-α）表达降低抑制了炎症反应，从而显著提高了随意皮瓣的存活率。总之，本研究突出了6BQ纳米颗粒在提高随意皮瓣存活率方面的潜力，为伤口修复提供了一种新的治疗策略。
