Liu Guei-Sheung, Chen Huai-An, Chang Che-Yi, Chen Yin-Ju, Wu Yu-Yi, Widhibrata Ariel, Yang Ya-Han, Hsieh Erh-Hsuan, Delila Liling, Lin I-Chan, Burnouf Thierry, Tseng Ching-Li
Centre for Eye Research Australia, Royal Victorian Eye and Ear Hospital, East Melbourne, Australia; Graduate Institute of Biomedical Materials and Tissue Engineering, College of Biomedical Engineering, Taipei Medical University, Shuang-Ho Campus, New Taipei City, Taiwan; Ophthalmology, Department of Surgery, University of Melbourne, East Melbourne, Australia; Menzies Institute for Medical Research, University of Tasmania, Hobart, Australia.
Graduate Institute of Biomedical Materials and Tissue Engineering, College of Biomedical Engineering, Taipei Medical University, Shuang-Ho Campus, New Taipei City, Taiwan.
Biomaterials. 2025 Aug;319:123205. doi: 10.1016/j.biomaterials.2025.123205. Epub 2025 Feb 24.
Platelet-derived extracellular vesicles (PEVs) have drawn attention due to their multifunctionality, ease of procurement, and abundant supply from clinical-grade platelet concentrates. PEVs can be readily endocytosed due to their lipid bilayer membrane and nanoscale structure, enhancing the bioavailability and efficacy of their therapeutic effects. PEVs also contain various trophic factors that enhance their effectiveness as therapeutic agents. Given that nanomedicine provides benefits over traditional treatments for eye diseases by surpassing physical ocular barriers, PEVs combined with the anti-angiogenic agent, kaempferol (KM), were assessed for their capacity to inhibit abnormal blood vessel formation in the cornea. Characterization of the nanoparticles suggested the successful preparation of KM-loaded PEVs (PEV-KM) with a mean diameter of approximately 160 nm and an encapsulation efficiency of around 61 %. PEV-KM was effectively internalized into human vascular endothelial cells, resulting in inhibited function, as evidenced by lower wound closure rates, decreased tube formation capacity, and downregulation of angiogenesis-related gene expression. Moreover, prolonged ocular retention was observed following the topical application of PEV and PEV-KM in mouse eyes. In an alkali-burned corneal neovascularization (CoNV) mouse model, PEV (1 %) was found to decrease vessel formation in the injured cornea. However, the combination of PEV and KM (1 % PEV with KM 6 μg/mL) showed an even stronger effect in inhibiting CoNV and decreasing the expression of proangiogenic and inflammatory cytokines. Overall, our data suggests that the topical administration of PEVs, either alone or alongside KM (PEV-KM), is a promising therapy for the management of CoNV.
血小板衍生的细胞外囊泡（PEVs）因其多功能性、易于获取以及临床级血小板浓缩物的丰富供应而受到关注。由于其脂质双分子层膜和纳米级结构，PEVs能够很容易地被内吞，从而提高其治疗效果的生物利用度和功效。PEVs还含有各种营养因子，增强了它们作为治疗剂的有效性。鉴于纳米医学通过突破眼部物理屏障为眼科疾病的传统治疗带来了优势，我们评估了PEVs与抗血管生成剂山奈酚（KM）联合使用对抑制角膜异常血管形成的能力。纳米颗粒的表征表明成功制备了平均直径约为160 nm、包封率约为61%的载KM的PEVs（PEV-KM）。PEV-KM能够有效地内化进入人血管内皮细胞，导致其功能受到抑制，较低的伤口闭合率、降低的管腔形成能力以及血管生成相关基因表达的下调都证明了这一点。此外，在小鼠眼部局部应用PEV和PEV-KM后观察到其眼部滞留时间延长。在碱烧伤角膜新生血管化（CoNV）小鼠模型中，发现PEV（1%）可减少受损角膜中的血管形成。然而，PEV与KM联合使用（1% PEV与6 μg/mL KM）在抑制CoNV和降低促血管生成和炎性细胞因子表达方面显示出更强的效果。总体而言，我们的数据表明，单独或与KM联合局部应用PEVs（PEV-KM）是一种有前景的CoNV治疗方法。
