联合使用聚乙二醇化脂质体中的吉西他滨和盐酸莫米松,对结直肠癌的治疗效果进行增强。
Co-delivery of gemcitabine and salinomycin in PEGylated liposomes for enhanced anticancer efficacy against colorectal cancer.
发表日期:2022 Dec 15
作者:
Lucia Ruxandra Tefas, Ioana Toma, Alina Sesarman, Manuela Banciu, Ancuta Jurj, Ioana Berindan-Neagoe, Lucia Rus, Rares Stiufiuc, Ioan Tomuta
来源:
JOURNAL OF LIPOSOME RESEARCH
摘要:
结直肠癌仍然是发达国家和新兴国家中导致患病率和死亡率的主要原因之一。癌瘤干细胞(CSC)是肿瘤细胞内的一种具有干细胞特性的亚群细胞,被认为负责肿瘤的初始、生长、复发和治疗失败。最近,人们已经明确了除了CSC外,非CSC也必须被消除才能成功根除癌症。药物输送系统已广泛应用于增强药物疗效。在本研究中,我们将一种选择性抗CSC药物盐酸盐霉素(SAL)和一种传统的抗癌药物吉西他滨(GEM)共同载入脂质体中,并测试其最佳治疗疗效。我们采用实验设计方法开发和优化GEM和SAL的脂质体输送系统。我们评估了脂质体的抗增殖效果在SW-620人类结肠癌细胞中。GEM和SAL载药脂质体的粒度、聚散度、电位和药物含量均达到了适当的水平。体外释放研究表明,GEM和SAL从脂质体中持续释放72小时。此外,在一个生物介质(FBS)中经过1个月的时间也没有发现脂质体聚集的迹象。载药脂质体的体外细胞毒性效果比单一GEM无论是自由还是脂质体形式的效果都要优越。使用载药脂质体共同疗法的GEM和SAL可以成为应对结直肠癌的有希望的策略。
Colorectal cancer remains one of the major causes of morbidity and mortality in both developed and emerging countries. Cancer stem cells (CSCs) are a subpopulation of cells within the tumor mass harboring stem cell characteristics, considered responsible for tumor initiation, growth, relapse, and treatment failure. Lately, it has become clear that both CSCs and non-CSCs have to be eliminated for the successful eradication of cancer. Drug delivery systems have been extensively employed to enhance drug efficacy. In this study, salinomycin (SAL), a selective anti-CSC drug, and gemcitabine (GEM), a conventional anticancer drug, were co-loaded in liposomes and tested for optimal therapeutic efficacy. We employed the Design of Experiments approach to develop and optimize a liposomal delivery system for GEM and SAL. The antiproliferative effect of the liposomes was evaluated in SW-620 human colorectal cancer cells. The GEM and SAL-loaded liposomes exhibited adequate size, polydispersity, zeta potential, and drug content. The in vitro release study showed a sustained release of GEM and SAL from the liposomes over 72 h. Moreover, no sign of liposome aggregation was seen over 1 month and in a biological medium (FBS). The in vitro cytotoxic effects of the co-loaded liposomes were superior to that of single GEM either in free or liposomal form. The combination therapy using GEM and SAL co-loaded in liposomes could be a promising strategy for tackling colorectal cancer.