Department of Radiology, XD Group Hospital, Xi'an City, Shaanxi Province, 710077, China.
Department of CT Room, Dongying People's Hospital, Dongying City, Shandong Province, 257091, China.
Biomed Pharmacother. 2020 Sep;129:110371. doi: 10.1016/j.biopha.2020.110371. Epub 2020 Jun 18.
Lung cancer still remains a leading cause of cancer mortality in the world. Obatoclax mesylate (OM), a B cell chronic lymphocytic leukemia/lymphoma 2 (Bcl-2) family antagonist, is a potential antitumor drug. However, its poor aqueous solubility restricts its clinical application. Although these inherent defects, nanotechnology can be used to improve the solubility and tumor target of OM, promoting its antitumor efficiency. In the present study, the poly(lactic-coglycolic acid) (PLGA) was used and combined with red blood-cell membrane (RBCm) to explore if OM-loaded RBCm nanoparticles could improve the antitumor efficacy of OM for the treatment of lung cancer with relatively lower side effects compared with the free OM. The good physicochemical stability of the prepared RBCm-OM/PLGA nanoparticles was confirmed, and the optimal size of 153 nm was screened out, along with sustained drug release behavior. We found that RBCm-OM/PLGA nanoparticles effectively reduced the proliferation of lung cancer cells. Additionally, RBCm-OM/PLGA nanoparticles considerably induced apoptosis in lung cancer cells by reducing Bcl-2 expression levels, accompanied with the improved Cyto-c releases in cytoplasm and Caspase-3 activation. Mitochondrial membrane potential was also obviously impaired in lung cancer cells incubated with RBCm-OM/PLGA nanoparticles. Compared with free OM, RBCm-OM/PLGA nanoparticles could greatly prolong the drug circulation time in vivo and upgraded the drug concentration accumulated in tumor tissue. Furthermore, RBCm-OM/PLGA nanoparticles exerted stronger antitumor efficacy in vivo against lung cancer progression with superior safety. Therefore, RBCm-OM/PLGA nanoparticles provided new potential for lung cancer therapy with the improved safety and therapeutic effect.
肺癌仍然是全球癌症死亡的主要原因。奥巴妥克拉克斯甲酯（OM）是一种 B 细胞慢性淋巴细胞白血病/淋巴瘤 2（Bcl-2）家族拮抗剂，是一种有潜力的抗肿瘤药物。然而，其较差的水溶性限制了其临床应用。尽管存在这些固有缺陷，但纳米技术可用于提高 OM 的水溶性和肿瘤靶向性，从而提高其抗肿瘤效率。在本研究中，使用聚（乳酸-羟基乙酸）（PLGA）并结合红细胞膜（RBCm），以探索载 OM 的 RBCm 纳米粒是否可以提高 OM 的抗肿瘤疗效，与游离 OM 相比，其副作用相对较低，用于治疗肺癌。所制备的 RBCm-OM/PLGA 纳米粒具有良好的物理化学稳定性，筛选出最佳粒径为 153nm，具有持续的药物释放行为。我们发现 RBCm-OM/PLGA 纳米粒有效抑制了肺癌细胞的增殖。此外，RBCm-OM/PLGA 纳米粒通过降低 Bcl-2 表达水平，显著诱导肺癌细胞凋亡，同时伴有细胞质中 Cyto-c 的释放和 Caspase-3 的激活增加。线粒体膜电位也明显受损。与游离 OM 相比，RBCm-OM/PLGA 纳米粒能大大延长体内药物循环时间，并提高肿瘤组织中药物的蓄积浓度。此外，RBCm-OM/PLGA 纳米粒在体内对肺癌进展的抗肿瘤疗效更强，安全性更高。因此，RBCm-OM/PLGA 纳米粒为提高安全性和治疗效果的肺癌治疗提供了新的潜力。
