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纳米气泡携带 siRNA 联合超声靶向破坏治疗脑胶质瘤的疗效。

The therapeutic effect in gliomas of nanobubbles carrying siRNA combined with ultrasound-targeted destruction.

机构信息

Department of Ultrasound Diagnosis, Tang Du Hospital, Fourth Military Medical University, Xi'an 710038, China,

General Hospital of Tibet Military Command, Lhasa, Tibet Autonomous Region, 850007, China.

出版信息

Int J Nanomedicine. 2018 Oct 24;13:6791-6807. doi: 10.2147/IJN.S164760. eCollection 2018.

DOI:10.2147/IJN.S164760

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC6205539/

Abstract

BACKGROUND

Nanobubbles (NBs) combined with ultrasound-targeted destruction (UTD) have become promising potential carriers for drug or siRNA delivery. Due to their nano-size, NBs could penetrate tumor blood vessels and accumulate in intercellular spaces so that "sonoporation" induced by UTD would act directly on the tumor cells to increase cell membrane permeability.

METHODS

Based on the successful the fabrication of NBs, we synthesized NBs carrying siRNA (NBs-siRNA) by using a biotin-streptavidin system. We then utilized ultrasound irradiation (UI)-targeted NBs-siRNA to improve siRNA transfection and achieve the inhibition of glioma growth.

RESULTS

NBs as carriers combined with UI effectively enhanced siRNA transfection and the effect of silencing targeted genes in vitro. Additionally, a better therapeutic effect was shown in the NBs-siRNA with UI group in vivo compared with that of microbubbles (MBs) with UI or NBs-siRNA without UI.

CONCLUSION

These results indicated that NBs combined with UTD might be an ideal delivery vector for siRNA to achieve the noninvasive treatment of glioma.

摘要

背景

纳米气泡（NBs）与超声靶向破坏（UTD）结合已成为药物或 siRNA 传递的有前途的潜在载体。由于其纳米尺寸，NBs 可以穿透肿瘤血管并在细胞间隙中积聚，因此 UTD 诱导的“声孔”将直接作用于肿瘤细胞，增加细胞膜通透性。

方法

基于 NBs 的成功制备，我们通过生物素-链霉亲和素系统合成了携带 siRNA 的 NBs（NBs-siRNA）。然后，我们利用超声辐射（UI）靶向 NBs-siRNA 来提高 siRNA 的转染效率并实现对胶质瘤生长的抑制。

结果

作为载体的 NBs 与 UI 联合使用可有效增强 siRNA 的转染效率，并在体外沉默靶向基因的效果。此外，与 UI 微泡（MBs）或无 UI 的 NBs-siRNA 相比，NBs-siRNA 与 UI 联合使用具有更好的体内治疗效果。

结论

这些结果表明，NBs 与 UTD 结合可能是 siRNA 的理想递药载体，可实现对胶质瘤的非侵入性治疗。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e636/6205539/1d4a3718c792/ijn-13-6791Fig10.jpg

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e636/6205539/cf32502a5950/ijn-13-6791Fig1.jpg

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e636/6205539/f50e9f2a26e4/ijn-13-6791Fig2.jpg

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e636/6205539/2e8a6472baac/ijn-13-6791Fig3.jpg

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e636/6205539/c31484bef6a1/ijn-13-6791Fig4.jpg

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e636/6205539/c0a76e141e46/ijn-13-6791Fig5.jpg

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e636/6205539/0ae853b446d0/ijn-13-6791Fig6.jpg

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e636/6205539/1b4f9092ab40/ijn-13-6791Fig7.jpg

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e636/6205539/0ec37e538df3/ijn-13-6791Fig8.jpg

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e636/6205539/9b5e183e9ea1/ijn-13-6791Fig9.jpg

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e636/6205539/1d4a3718c792/ijn-13-6791Fig10.jpg

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e636/6205539/cf32502a5950/ijn-13-6791Fig1.jpg

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e636/6205539/f50e9f2a26e4/ijn-13-6791Fig2.jpg

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e636/6205539/2e8a6472baac/ijn-13-6791Fig3.jpg

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e636/6205539/c31484bef6a1/ijn-13-6791Fig4.jpg

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e636/6205539/c0a76e141e46/ijn-13-6791Fig5.jpg

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e636/6205539/0ae853b446d0/ijn-13-6791Fig6.jpg

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e636/6205539/1b4f9092ab40/ijn-13-6791Fig7.jpg

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e636/6205539/0ec37e538df3/ijn-13-6791Fig8.jpg

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e636/6205539/9b5e183e9ea1/ijn-13-6791Fig9.jpg

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e636/6205539/1d4a3718c792/ijn-13-6791Fig10.jpg

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