Enzyme-Responsive Nanoparticles for Dexamethasone Targeted Delivery to Treat Inflammation in Diabetes.
Enzyme-Responsive Nanoparticles for Dexamethasone Targeted Delivery to Treat Inflammation in Diabetes.
复制标题
用于地塞米松靶向递送以治疗糖尿病炎症的酶响应纳米颗粒。
DOI：
10.1002/adhm.202301053
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发表时间：
2023
影响因子：
10
通讯作者：
Rosen,Eyal
中科院分区：
文献类型：
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作者：
Schiffmann,Nathan;Liang,Yifei;Nemcovsky,CarlosE;Almogy,Michal;Halperin-Sternfeld,Michal;Gianneschi,NathanC;Adler-Abramovich,Lihi;Rosen,Eyal
糖尿病是一种全球流行病，伴随着伤口愈合受损、持续感染风险增加和对标准治疗的耐药性。因此，迫切需要开发新的方法来特异性靶向治疗受影响的组织并提高治疗效果。这项研究旨在利用酶反应纳米颗粒靶向递送抗炎药物地塞米松来治疗糖尿病炎症。这些纳米颗粒是由荧光标记的、装载地塞米松的肽聚合物两亲体组装而成的。将纳米颗粒注射到糖尿病大鼠颅骨骨膜下植入的标记胶原膜附近。植入后，胶原膜的吸收与炎症有关，特别是在高血糖个体中。纳米颗粒在炎症组织中表现出强大而持久的积聚，在经历了形态转换后成为微尺度聚集体。与注射游离地塞米松和无反应纳米颗粒的对照组相比，反应性纳米颗粒处理的大鼠的剩余胶原膜面积显著增加，炎症细胞浸润减少。这些因素表明在减少炎症方面的治疗效果有所改善。这些结果证明了酶反应纳米颗粒作为治疗糖尿病和其他炎症性伤口的靶向递送载体的潜在用途。
Diabetes is a global epidemic accompanied by impaired wound healing and increased risk of persistent infections and resistance to standard treatments. Therefore, there is an immense need to develop novel methods to specifically target therapeutics to affected tissues and improve treatment efficacy. This study aims to use enzyme‐responsive nanoparticles for the targeted delivery of an anti‐inflammatory drug, dexamethasone, to treat inflammation in diabetes. These nanoparticles are assembled from fluorescently‐labeled, dexamethasone‐loaded peptide‐polymer amphiphiles. The nanoparticles are injected in vivo, adjacent to labeled collagen membranes sub‐periosteally implanted on the calvaria of diabetic rats. Following their implantation, collagen membrane resorption is linked to inflammation, especially in hyperglycemic individuals. The nanoparticles show strong and prolonged accumulation in inflamed tissue after undergoing a morphological switch into microscale aggregates. Significantly higher remaining collagen membrane area and less inflammatory cell infiltration are observed in responsive nanoparticles‐treated rats, compared to control groups injected with free dexamethasone and non‐responsive nanoparticles. These factors indicate improved therapeutic efficacy in inflammation reduction. These results demonstrate the potential use of enzyme‐responsive nanoparticles as targeted delivery vehicles for the treatment of diabetic and other inflammatory wounds.