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GE11-Directed Functional Polymersomal Doxorubicin as an Advanced Alternative to Clinical Liposomal Formulation for Ovarian Cancer Treatment
Molecular Pharmaceutics ( IF 4.9 ) Pub Date : 2018-03-23 00:00:00 , DOI: 10.1021/acs.molpharmaceut.8b00024
Yan Zou 1, 2 , Yifeng Xia 1 , Fenghua Meng 1 , Jian Zhang 1 , Zhiyuan Zhong 1
Affiliation  

Ovarian cancer as a recurrent disease is often refractory to treatment including pegylated liposomal doxorubicin hydrochloride (Lipo-Dox). Here, GE11 peptide-modified reversibly cross-linked polymersomal doxorubicin (GE11-PS-Dox) was investigated as an advanced treatment for SKOV3 human ovarian tumors, which overexpress epidermal growth factor receptor (EGFR). The in vitro experiments using SKOV3 cancer cells demonstrated that GE11-PS-Dox induced obviously higher cellular uptake, Dox delivery to the nuclei, and antitumor activity than the nontargeted PS-Dox and Lipo-Dox controls. In vivo biodistribution experiments displayed 2.5-fold higher tumor accumulation for GE11-PS-Dox as compared to Lipo-Dox. Notably, GE11-PS-Dox could effectively suppress the progression of SKOV3 tumors and cause little adverse effects at 12 mg of Dox equiv/kg, leading to a remarkably increased survival rate of 100% over 78 days. In contrast, continued tumor growth and body weight loss were discerned for Lipo-Dox treated mice at 6 mg of Dox equiv/kg. Moreover, a single dose of GE11-PS-Dox at 60 mg of Dox equiv/kg showed also effective treatment and low toxicity toward SKOV3-tumor bearing mice. GE11-directed reversibly cross-linked polymersomal doxorubicin has emerged as an advanced alternative to Lipo-Dox for treatment of EGFR-overexpressing ovarian cancers.

中文翻译:

GE11指导的功能性聚合物阿霉素作为卵巢癌治疗的临床脂质体制剂的替代品

作为复发性疾病的卵巢癌通常难以治疗,包括聚乙二醇化脂质体阿霉素盐酸盐(Lipo-Dox)。在这里,GE11肽修饰的可逆交联的多柔比星阿霉素(GE11-PS-Dox)被研究为过度表达表皮生长因子受体(EGFR)的SKOV3人卵巢肿瘤的高级治疗方法。在体外实验中使用证明,GE11-PS-Dox的明显更高的诱导细胞摄取霉素递送至核,并且比非靶向PS-Dox和前列-DOX控制抗肿瘤活性SKOV3癌细胞。体内生物分布实验显示,与Lipo-Dox相比,GE11-PS-Dox的肿瘤蓄积高2.5倍。值得注意的是,GE11-PS-Dox可以有效地抑制SKOV3肿瘤的进展,并且在12 mg Dox当量/ kg时几乎没有不良反应,从而在78天内显着提高了100%的存活率。相反,对于接受Lipo-Dox处理的小鼠,当Dox当量为6 mg / kg时,可观察到持续的肿瘤生长和体重减轻。此外,单剂量的GE11-PS-Dox剂量为60 mg Dox equiv / kg时,也显示出对SKOV3荷瘤小鼠的有效治疗和低毒性。GE11定向可逆交联的多柔比星阿霉素已成为Lipo-Dox治疗EGFR过表达的卵巢癌的一种先进替代方法。
更新日期:2018-03-23
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