Nie Qiang, Li Chenwen, Wang Yu, Hu Yi, Pu Wendan, Zhang Qixiong, Cai Jiajun, Lin Yongyao, Li Gang, Wang Chenping, Li Lanlan, Dou Yin, Zhang Jianxiang
Department of Pharmaceutics, College of Pharmacy, Third Military Medical University (Army Medical University), Chongqing 400038, China.
Department of Radiology, Chongqing University Cancer Hospital & Chongqing Cancer Institute & Chongqing Cancer Hospital, Chongqing 400030, China.
Acta Pharm Sin B. 2023 Jan;13(1):390-409. doi: 10.1016/j.apsb.2022.07.013. Epub 2022 Jul 20.
Uncontrolled and persistent inflammation is closely related to numerous acute and chronic diseases. However, effective targeting delivery systems remain to be developed for precision therapy of inflammatory diseases. Herein we report a novel strategy for engineering inflammation-accumulation nanoparticles phenolic functionalization. Different phenol-functionalized nanoparticles were first developed, which can undergo aggregation upon triggering by the inflammatory/oxidative microenvironment. Phenolic compound-decorated poly (lactideglycolide) nanoparticles, in particular tyramine (Tyr)-coated nanoparticles, showed significantly enhanced accumulation at inflammatory sites in mouse models of colitis, acute liver injury, and acute lung injury, mainly resulting from cross-linking and tissue anchoring of nanoparticles triggered by local myeloperoxidase and reactive oxygen species. By combining a cyclodextrin-derived bioactive material with Tyr decoration, a multifunctional nanotherapy (TTN) was further developed, which displayed enhanced cellular uptake, anti-inflammatory activities, and inflammatory tissue accumulation, thereby affording amplified therapeutic effects in mice with colitis or acute liver injury. Moreover, TTN can serve as a bioactive and inflammation-targeting nanoplatform for site-specifically delivering a therapeutic peptide to the inflamed colon post oral administration, leading to considerably potentiated efficacies. Preliminary studies also revealed good safety of orally delivered TTN. Consequently, Tyr-based functionalization is promising for inflammation targeting amplification and therapeutic potentiation of nanotherapies.
不受控制的持续性炎症与众多急慢性疾病密切相关。然而，针对炎症性疾病的精准治疗，仍有待开发有效的靶向递送系统。在此，我们报告了一种构建炎症聚集纳米颗粒的新策略——酚功能化。首先制备了不同的酚功能化纳米颗粒，它们可在炎症/氧化微环境触发下发生聚集。酚类化合物修饰的聚（丙交酯-乙交酯）纳米颗粒，特别是酪胺（Tyr）包被的纳米颗粒，在结肠炎、急性肝损伤和急性肺损伤小鼠模型的炎症部位积累显著增强，这主要是由于局部髓过氧化物酶和活性氧触发纳米颗粒发生交联并锚定在组织中。通过将环糊精衍生的生物活性材料与Tyr修饰相结合，进一步开发了一种多功能纳米疗法（TTN），它表现出增强的细胞摄取、抗炎活性和炎症组织积累，从而在结肠炎或急性肝损伤小鼠中提供增强的治疗效果。此外，TTN可作为一种生物活性且靶向炎症的纳米平台，用于口服给药后将治疗性肽特异性递送至炎症结肠部位，从而显著增强疗效。初步研究还显示口服TTN具有良好的安全性。因此，基于Tyr的功能化在纳米疗法的炎症靶向增强和治疗增效方面具有广阔前景。
