含有葫芦素 B 的黄瓜衍生纳米囊泡用于非小细胞肺癌治疗。
Cucumber-Derived Nanovesicles Containing Cucurbitacin B for Non-Small Cell Lung Cancer Therapy.
机构信息
School of Pharmacy, Fujian Medical University, Fuzhou, Fujian Province, 350108, People's Republic of China.
Fujian Key Laboratory of Drug Target Discovery and Structural and Functional Research, Fujian Medical University, Fuzhou, Fujian Province, 350108, People's Republic of China.
出版信息
Int J Nanomedicine. 2022 Aug 10;17:3583-3599. doi: 10.2147/IJN.S362244. eCollection 2022.
PURPOSE
In recent years, a variety of nanoparticles with excellent anticancer and delivery properties have emerged for cancer therapy. However, potential toxicity, high production cost and complex preparation procedures have been obstacles to their use in biomedicine. Here, we obtained cucumber-derived nanovesicles (CDNVs) at high yield and low cost by simple juicing and ultracentrifugation. The anticancer effects of CDNVs were evaluated in vitro and in vivo.
METHODS
Transmission electron microscope, nanoparticle tracking analysis and laser particle size analysis were used to characterize the morphology, diameter and zeta potential of CDNVs, respectively. The anticancer effects of CDNVs in vitro were evaluated by MTT and apoptosis assays. The mechanism was further explored by measuring the protein levels of signal transducer and activator of transcription 3 pathway, reactive oxygen species, cell cycle distribution and caspase activity. In-vivo anticancer efficacy was evaluated by measuring tumor volume and weight of mice in three different treatment groups (CDNVs, cucurbitacin B and PBS).
RESULTS
CDNVs inhibited proliferation of human non-small cell lung cancer cells by suppressing signal transducer and activator of transcription 3 activation, generating reactive oxygen species, promoting cell cycle arrest, and activating the caspase pathway. These CDNVs exhibited strong anticancer effects both in vitro and in vivo, and reduced the rate of tumor growth without obvious toxicity to mouse visceral organs. Compared with an equivalent dose of cucurbitacin B, CDNVs exerted stronger anticancer effects in vitro and in vivo.
CONCLUSION
These results demonstrate that CDNVs suppress tumor growth. This study addresses the development of cancer therapeutic drugs using plant-derived nanovesicles that are cost-efficient, simple to produce in high yields, and provide an alternative approach to drug isolation that may help advance sustainability of medicinal plants.
目的
近年来,出现了多种具有优异抗癌和递药性能的纳米粒子,可用于癌症治疗。然而,潜在毒性、高生产成本和复杂的制备程序一直是其在生物医学中应用的障碍。在这里,我们通过简单的榨汁和超速离心获得了高产率和低成本的黄瓜衍生纳米囊泡(CDNVs)。评估了 CDNVs 的体内外抗癌作用。
方法
透射电子显微镜、纳米颗粒跟踪分析和激光粒度分析分别用于表征 CDNVs 的形态、直径和 zeta 电位。通过 MTT 和凋亡实验评估 CDNVs 的体外抗癌作用。通过测量信号转导和转录激活因子 3 通路、活性氧、细胞周期分布和半胱天冬酶活性的蛋白水平,进一步探讨其作用机制。通过测量三组不同治疗组(CDNVs、葫芦素 B 和 PBS)中小鼠的肿瘤体积和重量来评估体内抗癌疗效。
结果
CDNVs 通过抑制信号转导和转录激活因子 3 的激活、产生活性氧、促进细胞周期停滞和激活半胱天冬酶途径来抑制人非小细胞肺癌细胞的增殖。这些 CDNVs 在体外和体内均表现出很强的抗癌作用,降低了肿瘤生长速度,而对小鼠内脏器官没有明显毒性。与等效剂量的葫芦素 B 相比,CDNVs 在体外和体内均表现出更强的抗癌作用。
结论
这些结果表明 CDNVs 可抑制肿瘤生长。本研究利用成本效益高、易于高产的植物衍生纳米囊泡开发抗癌药物,为药物分离提供了一种替代方法,可能有助于推进药用植物的可持续性。