Prabhakar Ameya, Banerjee Rinti
Department of Biosciences and Bioengineering, Indian Institute of Technology Bombay, Mumbai 400076, India.
ACS Omega. 2019 Sep 12;4(13):15567-15580. doi: 10.1021/acsomega.9b01924. eCollection 2019 Sep 24.
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.
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。