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载有靶向 siRNA 的 PD-L1 外泌体及其对肺癌的功能评估。

A targeted siRNA-loaded PDL1-exosome and functional evaluation against lung cancer.

机构信息

Department of Thoracic Surgery, The Second Affiliated Hospital of Fujian Medical University, Quanzhou, China.

Department of Thoracic Surgery, Fujian Medical University Union Hospital, Key Laboratory of Cardio-Thoracic Surgery (Fujian Medical University), Fuzhou, China.

出版信息

Thorac Cancer. 2022 Jun;13(11):1691-1702. doi: 10.1111/1759-7714.14445. Epub 2022 May 11.

Abstract

BACKGROUND

As an endocytic nanosicle involved in intercellular communication, an exosome can efficiently deliver drugs from one cell to another and deliver therapeutic short interfering RNA (siRNA) to target cells. This is conducive to gene therapy for cancers. In this study, an exosome was used as the siRNA-loaded substrate to prepare a targeted siRNA-loaded PD-L1 exosome and evaluate its function against lung cancer.

METHODS

The optimal preparation process and binding ratio of the targeted nanovesicle/siRNA complex was determined by detecting the particle size, potential, and other physical parameters in combination with cell binding and uptake capacity of exosome complexes. The biological cell behavior of targeted exosome nanosicles was evaluated through cytotoxicity, apoptosis, and the cell uptake capacity.

RESULTS

A targeted exosome nanovesicle capable of loading siRNA and characterized with low toxicity, high loading rate, and the ability to be used for targeted tumor cell gene therapy was constructed.

CONCLUSION

The PD-L1 targeting exosome can be used as an efficient siRNA delivery carrier, which is an efficient and safe nanocarrier for tumor targeted gene therapy.

摘要

背景

作为一种参与细胞间通讯的内吞纳米囊泡,外泌体能够有效地将药物从一个细胞递送到另一个细胞,并将治疗性短干扰 RNA(siRNA)递送到靶细胞。这有助于癌症的基因治疗。在本研究中,外泌体被用作负载 siRNA 的底物,制备靶向 PD-L1 负载 siRNA 的外泌体,并评估其对肺癌的作用。

方法

通过检测粒径、电位等物理参数,并结合外泌体复合物的细胞结合和摄取能力,确定靶向纳米囊泡/siRNA 复合物的最佳制备工艺和结合比。通过细胞毒性、细胞凋亡和细胞摄取能力来评估靶向外泌体纳米囊泡的生物细胞行为。

结果

构建了一种能够负载 siRNA 且具有低毒性、高载药率和用于靶向肿瘤细胞基因治疗能力的靶向外泌体纳米囊泡。

结论

PD-L1 靶向外泌体可用作有效的 siRNA 递送载体,是一种高效、安全的肿瘤靶向基因治疗的纳米载体。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/449d/9161323/278ce4d6d221/TCA-13-1691-g007.jpg

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