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用于持续释放抗PD-L1抗体的乙碘油乳剂。

Ethiodized Oil Emulsion for Sustained Release of Anti-PD-L1 Antibodies.

作者信息

Satomura Hiroki, Kimura Yasushi, Kennoki Norifumi, Tomotake Kosuke, Yano Hiroki, Koretsune Yuji, Katayama Daisuke, Tanaka Kaishu, Ono Yusuke, Higashihara Hiroki, Tomiyama Noriyuki

机构信息

Department of Diagnostic and Interventional Radiology, Osaka University Graduate School of Medicine, Suita, Osaka, Japan. Electronic address: https://twitter.com/j_irist.

Department of High Precision Image-guided Percutaneous Intervention, Osaka University Graduate School of Medicine, Suita, Osaka, Japan.

出版信息

J Vasc Interv Radiol. 2025 May;36(5):861-868.e2. doi: 10.1016/j.jvir.2025.01.040. Epub 2025 Jan 23.

Abstract

PURPOSE

To develop and assess an ethiodized oil (Lipiodol) Pickering emulsion containing anti-programmed cell death ligand 1 (PD-L1) antibodies through in vitro experiments.

MATERIALS AND METHODS

The emulsion was created by combining ethiodized oil with poly (lactic-co-glycolic acid) (PLGA) nanoparticles and anti-PD-L1 antibodies. Confocal laser microscopy was used to evaluate the encapsulation of the antibodies within the Pickering emulsion. To assess the stability, the emulsion was visually examined, and droplet sizes were measured under a light microscope. For the sustained release evaluation, the emulsion was introduced into saline and incubated in a shaking bath, after which the supernatant was collected over time. The concentration of anti-PD-L1 antibodies in the supernatant was determined using a bicinchoninic acid assay. Western blotting and flow cytometry were employed to confirm the functionality of the released antibodies. A conventional ethiodized oil emulsion was used as a control for comparison.

RESULTS

The anti-PD-L1 antibodies were encapsulated within the layer of PLGA nanoparticles, positioned at the interface between the water and oil phases, as confirmed by confocal laser microscopy. The ethiodized oil Pickering emulsion demonstrated long-term stability with significantly smaller droplet sizes (P < .001). Moreover, the emulsion facilitated a gradual and sustained release of the anti-PD-L1 antibodies over an 8-week period (P < .001). The antibodies released from the emulsion specifically targeted PD-L1.

CONCLUSIONS

This study demonstrated that ethiodized oil Pickering emulsions effectively encapsulate anti-PD-L1 antibodies and enable their sustained release, highlighting their potential as a therapeutic agent for primary and secondary liver cancers.

摘要

目的

通过体外实验研发并评估一种含抗程序性细胞死亡配体1(PD-L1)抗体的碘化油(碘油)皮克林乳液。

材料与方法

通过将碘化油与聚乳酸-羟基乙酸共聚物(PLGA)纳米颗粒及抗PD-L1抗体混合来制备乳液。采用共聚焦激光显微镜评估抗体在皮克林乳液中的包封情况。为评估稳定性,对乳液进行肉眼观察,并在光学显微镜下测量液滴大小。为进行缓释评估,将乳液加入盐水中并在摇床中孵育,之后随时间收集上清液。使用二辛可宁酸测定法测定上清液中抗PD-L1抗体的浓度。采用蛋白质免疫印迹法和流式细胞术确认释放抗体的功能。使用传统碘化油乳液作为对照进行比较。

结果

共聚焦激光显微镜证实,抗PD-L1抗体被包封在PLGA纳米颗粒层内,位于水相和油相的界面处。碘化油皮克林乳液表现出长期稳定性,液滴尺寸显著更小(P <.001)。此外,该乳液在8周内促进了抗PD-L1抗体的逐渐和持续释放(P <.001)。从乳液中释放的抗体特异性靶向PD-L1。

结论

本研究表明,碘化油皮克林乳液可有效包封抗PD-L1抗体并实现其持续释放,凸显了其作为原发性和继发性肝癌治疗药物的潜力。

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