Verteporfin-Loaded Bioadhesive Nanoparticles for the Prevention of Hypertrophic Scar
Verteporfin-Loaded Bioadhesive Nanoparticles for the Prevention of Hypertrophic Scar
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DOI：
10.1002/smtd.202301295
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发表时间：
2023-12-12
期刊：
影响因子：
12.4
通讯作者：
Xie，Julin
中科院分区：
文献类型：
--
作者：
Wang，Peng;Peng，Zhangwen;Xie，Julin
增生性瘢痕(HS)是一种常见的皮肤损伤并发症，但尚未得到满足。维替泊芬(VP)具有有效的纤维化和血管生成抑制作用，是一种理想的HS靶向治疗药物。然而，它的应用受到其副作用的限制，如对正常细胞的剂量依赖性细胞毒性。在此，成功研制了VP生物黏附纳米粒(VP/BNPS)，通过限制VP在病变部位缓慢而稳定地释放，而不是容易扩散到正常组织，从而减轻VP的副作用，增强其HS抑制作用。VP/BNPS对人增生性瘢痕成纤维细胞(HSFB)和真皮血管内皮细胞(HDVECs)的增殖、迁移、胶原沉积和血管形成有明显的抑制作用。在大鼠尾部HS模型中，VP/BNPS处理的HS表现出显著的瘢痕抑制，与游离VP或VP负载的非生物黏附纳米粒(VP/NNPs)注射相比几乎没有副作用。进一步对瘢痕组织连续切片的免疫荧光分析证实，VP/BNPS通过牢固地定位于瘢痕组织并持续释放针对HSFBS和HDVECs核Yes-Association Protein(NYAP)的VP，有效地抑制了胶原沉积和血管生成。这些发现共同表明，VP/BNPS可能是HS治疗的一种有前景的、技术上有优势的药物。
Hypertrophic scarring (HS) is a common skin injury complication with unmet needs. Verteporfin (VP) should be an ideal HS‐targeted therapeutic drug due to its efficient fibrosis and angiogenesis inhibitory abilities. However, its application is restricted by its side effects such as dose‐dependent cytotoxicity on normal cells. Herein, the bioadhesive nanoparticles encapsulated VP (VP/BNPs) are successfully developed to attenuate the side effects of VP and enhance its HS inhibition effects by limiting VP releasing slowly and stably in the lesion site but not diffusing easily to normal tissues. VP/BNPs displayed significant inhibition on the proliferation, migration, collagen deposition, and vessel formation of human hypertrophic scar fibroblasts (HSFBs) and dermal vascular endothelial cells (HDVECs). In a rat tail HS model, VP/BNPs treated HS exhibits dramatic scar repression with almost no side effects compared with free VP or VP‐loaded non‐bioadhesive nanoparticles (VP/NNPs) administration. Further immunofluorescence analysis on scar tissue serial sections validated VP/BNPs effectively inhibited the collagen deposition and angiogenesis by firmly confined in the scar tissue and persistently releasing VP targeted to nucleus Yes‐associated protein (nYAP) of HSFBs and HDVECs. These findings collectively suggest that VP/BNPs can be a promising and technically advantageous agent for HS therapies.