School of Pharmacy, Changzhou University, Changzhou, Jiangsu 213164, PR China; Britton Chance Center for Biomedical Photonics at Wuhan National Laboratory for Optoelectronics-Hubei Bioinformatics and Molecular Imaging Key Laboratory, Department of Biomedical Engineering, College of Life Science and Technology, Huazhong University of Science and Technology, Wuhan 430074, Hubei, PR China.
School of Pharmacy, Changzhou University, Changzhou, Jiangsu 213164, PR China.
Int J Biol Macromol. 2022 Sep 30;217:55-65. doi: 10.1016/j.ijbiomac.2022.07.021. Epub 2022 Jul 9.
Infection-induced chronic wounds cause prolonged pains, a high risk of amputation, and even increased mortality in immunocompromised patients. Here we report an antibacterial microneedle (MN) patch, which features high degradability in biological fluids and gelatinase-responsive release of an antibacterial photothermal peptide AMP-Cypate. We first synthesize gelatin nanoparticles (GNPs) and then conjugate the AMP-Cypate to afford composite AMP-Cypate@GNPs. The proteinaceous nanoparticles can responsively release AMP-Cypate in the presence of gelatinase, an enzyme secreted specifically by Staphylococcus aureus (S. aureus). AMP-Cypate@GNPs were then deposited in the tips of MNs fabricated by PVP and recombinant human type III collagen (Col III) to devise the antibacterial MN/AMP-Cypate@GNP patches. When applied to the infection site, MNs break through the epidermis and the stratum corneum, dissolve in the infected dermis, reach the bacterial colony or biofilm, release AMP-Cypate@GNPs, and exert a gelatinase-responsive photothermal therapy under near-infrared (NIR) irradiation to kill the pathogen S. aureus. In a rat model of staphylococcal infection-induced chronic wounds mimicking the condition of diabetic foot ulcer, the antibacterial MN/AMP-Cypate@GNP patches eradiated the bacterial infection and resulted in complete healing of the wounds, proving its potential application in the treatment of chronic wound infections and diabetic foot ulcers.
感染引起的慢性伤口会导致长期疼痛、截肢风险增加，甚至使免疫功能低下的患者死亡率增加。在这里，我们报告了一种抗菌微针 (MN) 贴片，它具有在生物流体中高降解性和明胶酶响应释放抗菌光热肽 AMP-Cypate 的特点。我们首先合成明胶纳米颗粒 (GNPs)，然后将 AMP-Cypate 缀合到明胶酶响应释放的 AMP-Cypate@GNPs 上。这种蛋白质纳米颗粒可以在明胶酶存在的情况下响应性地释放 AMP-Cypate，明胶酶是金黄色葡萄球菌 (S. aureus) 特异性分泌的一种酶。然后将 AMP-Cypate@GNPs 沉积在由 PVP 和重组人 III 型胶原蛋白 (Col III) 制成的 MN 尖端，设计出抗菌 MN/AMP-Cypate@GNP 贴片。当应用于感染部位时，MN 会穿透表皮和角质层，在感染的真皮中溶解，到达细菌菌落或生物膜，释放 AMP-Cypate@GNPs，并在近红外 (NIR) 照射下发挥明胶酶响应光热治疗作用，杀死病原菌 S. aureus。在模拟糖尿病足溃疡的金黄色葡萄球菌感染诱导的慢性伤口的大鼠模型中，抗菌 MN/AMP-Cypate@GNP 贴片消除了细菌感染，导致伤口完全愈合，证明了其在慢性伤口感染和糖尿病足溃疡治疗中的潜在应用。
