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用于癌症诊断成像和超声触发药物递送的纳米气泡脂质体复合物:一种诊疗一体化方法。

Nanobubble Liposome Complexes for Diagnostic Imaging and Ultrasound-Triggered Drug Delivery in Cancers: A Theranostic Approach.

作者信息

Prabhakar Ameya, Banerjee Rinti

机构信息

Department of Biosciences and Bioengineering, Indian Institute of Technology Bombay, Mumbai 400076, India.

出版信息

ACS Omega. 2019 Sep 12;4(13):15567-15580. doi: 10.1021/acsomega.9b01924. eCollection 2019 Sep 24.

Abstract

The ability of ultrasound contrast agents to enhance the cell membrane permeability in response to an ultrasound pulse has unveiled avenues to facilitate the delivery of a higher intracellular payload at target sites. In light of the above, we report the development of submicron-sized (528.7 ± 31.7 nm) nanobubble-paclitaxel liposome (NB-PTXLp) complexes for ultrasound imaging and ultrasound responsive drug delivery in cancer cells. With a paclitaxel entrapment efficiency of 85.4 ± 4.39%, the 200 nm-sized liposomes tethered efficiently (conjugation efficiency ∼98.7 ± 0.14%) with the nanobubbles to form conjugates. Sonoporation of MiaPaCa-2 cells upon treatment with nanobubbles and ultrasound enhanced cellular permeability, resulting in 2.5-fold higher uptake of liposomes in comparison to only liposome treatment. This manifested into more than 300-fold higher anticancer activity of NB-PTXLps in the presence of ultrasound in MiaPaCa-2, Panc-1, MDA-MB-231, and AW-8507 cell lines, compared to commercial formulation ABRAXANE. Also, the NB-PTXLp conjugates were found to exhibit echogenicity comparable to the commercial ultrasound contrast agent SonoVue. In addition, the developed nanobubbles were found to exhibit more than 1 week echogenic stability as opposed to 6 h stability of the commercially available ultrasound contrast agent SonoVue. Hence, the NB-PTXLps developed herein could prove to be a promising and minimally invasive theranostic platform for cancer treatments in the future.

摘要

超声造影剂响应超声脉冲增强细胞膜通透性的能力,为在靶位点促进更高细胞内药物负载量的递送开辟了途径。鉴于此,我们报道了用于癌细胞超声成像和超声响应药物递送的亚微米级(528.7±31.7 nm)纳米气泡-紫杉醇脂质体(NB-PTXLp)复合物的研发。紫杉醇包封率为85.4±4.39%,200 nm大小的脂质体与纳米气泡有效连接(偶联效率约为98.7±0.14%)形成偶联物。用纳米气泡和超声处理后,MiaPaCa-2细胞的声孔效应增强了细胞通透性,与仅用脂质体处理相比,脂质体摄取量提高了2.5倍。这表现为在超声存在下,NB-PTXLp在MiaPaCa-2、Panc-1、MDA-MB-231和AW-8507细胞系中的抗癌活性比商业制剂ABRAXANE高300多倍。此外,发现NB-PTXLp偶联物的回声性与商业超声造影剂SonoVue相当。另外,发现所研发的纳米气泡表现出超过1周的回声稳定性,而市售超声造影剂SonoVue的稳定性为6小时。因此,本文研发的NB-PTXLp可能在未来成为一种有前景的、微创的癌症治疗诊断平台。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/686a/6761614/6004cf59c664/ao9b01924_0001.jpg

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