The Fifth Affiliated Hospital, Key Laboratory of Molecular Target & Clinical Pharmacology, NMPA, and the State Key Laboratory of Respiratory Disease, The School of Pharmaceutical Sciences, Guangzhou Medical University, Guangzhou 511436, P.R. China.
State Key Laboratory of Quality Research in Chinese Medicine, Macau University of Science and Technology, Macau 999078, P.R. China.
ACS Nano. 2024 Aug 13;18(32):21009-21023. doi: 10.1021/acsnano.4c01900. Epub 2024 Aug 1.
Acute lung injury (ALI) and its severe form, acute respiratory distress syndrome (ARDS), induce high morbidity and mortality rates, which challenge the present approaches for the treatment of ALI/ARDS. The clinically used photosensitizer verteporfin (VER) exhibits great potential in the treatment of acute lung injury and acute respiratory distress syndrome (ALI/ARDS) by regulating macrophage polarization and reducing inflammation. Nevertheless, its hydrophobic characteristics, nonspecificity, and constrained bioavailability hinder its therapeutic efficacy. In this work, we developed a type of VER-cored artificial exosome (EVM), which was produced by using mesoporous silica nanoparticles (MSNs) to load VER, followed by the exocytosis of internalized VER-MSNs from mouse bone marrow-derived mesenchymal stem cells (mBMSCs) without further modification. Both and assessments confirmed the powerful anti-inflammation induced by EVM. EVM also showed significant higher accumulation to inflammatory lungs compared with healthy ones, which was beneficial to the treatment of ALI/ARDS. EVM improved pulmonary function, attenuated lung injury, and reduced mortality in ALI mice with high levels of biocompatibility, exhibiting a 5-fold higher survival rate than the control. This type of artificial exosome emitted near-infrared light in the presence of laser activation, which endowed EVM with trackable ability both and . Our work developed a type of clinically used photosensitizer-loaded artificial exosome with membrane integrity and traceability. To the best of our knowledge, this kind of intracellularly synthesized artificial exosome was developed and showed great potential in ALI/ARDS therapy.
急性肺损伤 (ALI) 及其严重形式急性呼吸窘迫综合征 (ARDS) 导致高发病率和死亡率，这对目前 ALI/ARDS 的治疗方法提出了挑战。临床上使用的光敏剂维替泊芬 (VER) 通过调节巨噬细胞极化和减少炎症，在治疗急性肺损伤和急性呼吸窘迫综合征 (ALI/ARDS) 方面显示出巨大的潜力。然而，其疏水性、非特异性和受限的生物利用度阻碍了其治疗效果。在这项工作中，我们开发了一种 VER 核人工外泌体 (EVM)，它是通过使用介孔硅纳米粒子 (MSNs) 装载 VER 制成的，然后从小鼠骨髓间充质干细胞 (mBMSCs) 内化的 VER-MSNs 中通过外排作用释放出来，而无需进一步修饰。和 评估都证实了 EVM 具有强大的抗炎作用。EVM 还显示出与健康肺相比对炎症肺的更高聚集，这有利于 ALI/ARDS 的治疗。EVM 改善了 ALI 小鼠的肺功能，减轻了肺损伤，降低了死亡率，具有较高的生物相容性，存活率比对照组高 5 倍。这种人工外泌体在激光激活下发出近红外光，赋予了 EVM 可追踪的能力，无论是 还是 。我们的工作开发了一种具有膜完整性和可追踪性的临床使用的光敏剂负载人工外泌体。据我们所知，这种细胞内合成的人工外泌体被开发出来，并显示出在 ALI/ARDS 治疗方面有很大的潜力。
