Abstract：
BACKGROUND: Esophageal cancer is one of the major cancers in China. Most patients with esophageal cancer are diagnosed at an advanced stage, and the 5 year survival rate is discouraging. Combined chemotherapy is a common method for the treatment of esophageal cancer.
METHODS: In this study, distearoyl phosphatidyl ethanolamine polyethylene glycol 2000 (DSPE-PEG2000) nanoliposomes (NLPs) encapsulating the anticancer drugs docetaxel (DOX) and oridonin (ORD) were prepared, and their ability to enhance the release of anticancer drugs was determined. The NLP system was characterized by transmission electron microscopy, particle size and encapsulation efficiency. In addition, the release characteristics and pharmacodynamics of these drugs were also studied in detail.
RESULTS: When the DOX/ORD ratio was 2:1, the higher proportion of DOX led to a stronger synergy effect. DOX/ORD NLPs were prepared by the high-pressure homogenization method and had a uniform spherical morphology. The mean particle size and polydispersity index were determined to be 246.4 and 0.163, respectively. The stability results showed that no significant change was observed in particle size, zeta potential, Encapsulation efficiency and dynamic light scattering for DOX/ORD NLPs during the observation period. The results of in vitro release illustrated that the acidic environment of tumor might be beneficial to drug release. The three-dimensional tumorsphere showed that DOX/ORD NLPs can reach the interior of tumor spheres, which destroys the structure of cells, resulting in irregular spherical tumor spheres. The in vivo study results indicated that DOX/ORD NLPs had an obvious targeting effect on subcutaneous tumors and have the potential to actively deliver drugs to tumor tissues. Terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) staining was used to detect apoptosis. The results showed that DOX/ORD NLP treatment could significantly induce apoptosis and inhibit tumor growth.
CONCLUSIONS: The DOX/ORD NLPs prepared in this study can enhance the anti-tumor activity, and are expected to be a promising co-delivery platform for the treatment of esophageal cancer.
METHODS: In this study, distearoyl phosphatidyl ethanolamine polyethylene glycol 2000 (DSPE-PEG2000) nanoliposomes (NLPs) encapsulating the anticancer drugs docetaxel (DOX) and oridonin (ORD) were prepared, and their ability to enhance the release of anticancer drugs was determined. The NLP system was characterized by transmission electron microscopy, particle size and encapsulation efficiency. In addition, the release characteristics and pharmacodynamics of these drugs were also studied in detail.
RESULTS: When the DOX/ORD ratio was 2:1, the higher proportion of DOX led to a stronger synergy effect. DOX/ORD NLPs were prepared by the high-pressure homogenization method and had a uniform spherical morphology. The mean particle size and polydispersity index were determined to be 246.4 and 0.163, respectively. The stability results showed that no significant change was observed in particle size, zeta potential, Encapsulation efficiency and dynamic light scattering for DOX/ORD NLPs during the observation period. The results of in vitro release illustrated that the acidic environment of tumor might be beneficial to drug release. The three-dimensional tumorsphere showed that DOX/ORD NLPs can reach the interior of tumor spheres, which destroys the structure of cells, resulting in irregular spherical tumor spheres. The in vivo study results indicated that DOX/ORD NLPs had an obvious targeting effect on subcutaneous tumors and have the potential to actively deliver drugs to tumor tissues. Terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) staining was used to detect apoptosis. The results showed that DOX/ORD NLP treatment could significantly induce apoptosis and inhibit tumor growth.
CONCLUSIONS: The DOX/ORD NLPs prepared in this study can enhance the anti-tumor activity, and are expected to be a promising co-delivery platform for the treatment of esophageal cancer.
摘要：
背景：食管癌是中国的主要恶性肿瘤之一。大多数食管癌患者被诊断为晚期，5年生存率令人沮丧。联合化疗是治疗食管癌的常用方法。
方法：在本研究中，制备了包裹抗癌药物多西他赛(DOX)和冬凌草甲素(ORD)的二硬脂酰磷脂酰乙醇胺聚乙二醇2000(DSPE-PEG2000)纳米脂质体(NLP),并确定了它们增强抗癌药物释放的能力。通过透射电子显微镜对NLP系统进行了表征，颗粒大小和包封效率。此外,还详细研究了这些药物的释放特性和药效学。
结果：当DOX/ORD比为2：1时，较高的DOX比例导致更强的协同作用。通过高压均质方法制备DOX/ORDNLP，并具有均匀的球形形貌。平均粒度和多分散指数分别测定为246.4和0.163。稳定性结果表明，颗粒尺寸没有明显变化，zeta电位,观察期间DOX/ORDNLP的封装效率和动态光散射。体外释放结果表明，肿瘤的酸性环境可能有利于药物的释放。三维肿瘤球显示DOX/ORDNLP可以到达肿瘤球内部，这破坏了细胞的结构，导致不规则的球形肿瘤球。体内研究结果表明，DOX/ORDNLPs对皮下肿瘤有明显的靶向作用，具有向肿瘤组织主动递药的潜力。末端脱氧核苷酸转移酶dUTP缺口末端标记(TUNEL)染色用于检测细胞凋亡。结果表明，DOX/ORDNLP治疗可显著诱导细胞凋亡，抑制肿瘤生长。
结论：本研究制备的DOX/ORDNLP可增强抗肿瘤活性，有望成为食管癌治疗的一个有前途的联合治疗平台。
方法：在本研究中，制备了包裹抗癌药物多西他赛(DOX)和冬凌草甲素(ORD)的二硬脂酰磷脂酰乙醇胺聚乙二醇2000(DSPE-PEG2000)纳米脂质体(NLP),并确定了它们增强抗癌药物释放的能力。通过透射电子显微镜对NLP系统进行了表征，颗粒大小和包封效率。此外,还详细研究了这些药物的释放特性和药效学。
结果：当DOX/ORD比为2：1时，较高的DOX比例导致更强的协同作用。通过高压均质方法制备DOX/ORDNLP，并具有均匀的球形形貌。平均粒度和多分散指数分别测定为246.4和0.163。稳定性结果表明，颗粒尺寸没有明显变化，zeta电位,观察期间DOX/ORDNLP的封装效率和动态光散射。体外释放结果表明，肿瘤的酸性环境可能有利于药物的释放。三维肿瘤球显示DOX/ORDNLP可以到达肿瘤球内部，这破坏了细胞的结构，导致不规则的球形肿瘤球。体内研究结果表明，DOX/ORDNLPs对皮下肿瘤有明显的靶向作用，具有向肿瘤组织主动递药的潜力。末端脱氧核苷酸转移酶dUTP缺口末端标记(TUNEL)染色用于检测细胞凋亡。结果表明，DOX/ORDNLP治疗可显著诱导细胞凋亡，抑制肿瘤生长。
结论：本研究制备的DOX/ORDNLP可增强抗肿瘤活性，有望成为食管癌治疗的一个有前途的联合治疗平台。
