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Nanostructure of Functional Larotaxel Liposomes Decorated with Guanine‐Rich Quadruplex Nucleotide–Lipid Derivative for Treatment of Resistant Breast Cancer
Small ( IF 13.0 ) Pub Date : 2021-01-31 , DOI: 10.1002/smll.202007391 Xueqi Li 1 , Jianwei Li 1, 2 , Jiarui Xu 1 , Kun Chen 1 , Zhan Zhang 1 , Jialun Duan 1 , Qian Luo 1 , Yafei Du 1 , Songyue Chen 1 , Ying Xie 1 , Wanliang Lu 1
Small ( IF 13.0 ) Pub Date : 2021-01-31 , DOI: 10.1002/smll.202007391 Xueqi Li 1 , Jianwei Li 1, 2 , Jiarui Xu 1 , Kun Chen 1 , Zhan Zhang 1 , Jialun Duan 1 , Qian Luo 1 , Yafei Du 1 , Songyue Chen 1 , Ying Xie 1 , Wanliang Lu 1
Affiliation
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Breast cancer is the most common malignant disease in women all over the world and its chemotherapy outcome is restricted by multidrug resistance. Here, a nanostructure by functional larotaxel liposomes decorated with guanine‐rich quadruplex nucleotide‐lipid derivative for treatment of resistant breast cancer is developed. The studies are performed on the resistant breast cancer cells and the cancer‐bearing mice. The nucleotide–lipid derivative (DSPE‐PEG2000‐C6‐GT28nt) is synthesized by introducing a hydrophobic hexyl linkage between GT‐28nt (containing 17 guanines and 11 thymidines) and DSPE‐PEG2000‐NHS, and is incorporated on the functional larotaxel liposomes for specific binding with nucleolin receptor on the resistant cancer cells. The studies demonstrate that the liposomes had long circulatory effect, targeted capability, and significant anticancer efficacy in resistant cancer‐bearing mice. The studies further reveal their action mechanism, consisting of blocking depolymerization of microtubules, arresting cell cycle, blocking JAK‐STAT signaling pathway, and inhibiting activity of antiapoptotic proteins. In conclusion, the functional larotaxel liposomes can be used for effective treatment of drug‐resistant breast cancer, and this study also offers a novel targeted nanomedicine based on nucleotide–lipid derivative.
中文翻译：
鸟嘌呤丰富的四链核苷酸脂质脂质修饰的功能性拉罗他赛脂质体的纳米结构，用于治疗抗性乳腺癌
乳腺癌是全世界女性中最常见的恶性疾病，其化疗结果受到多药耐药性的限制。在这里，开发了一种功能性拉罗他赛脂质体的纳米结构，该脂质体修饰有鸟嘌呤丰富的四链体核苷酸脂质衍生物，可用于治疗耐药性乳腺癌。该研究是针对耐药性乳腺癌细胞和荷瘤小鼠进行的。核苷酸-脂质衍生物（DSPE-PEG 2000 - C 6 - GT28nt）是通过在GT-28nt（包含17个鸟嘌呤和11个胸苷）和DSPE-PEG 2000之间引入疏水己基键合成的-NHS，并结合在功能性紫杉醇脂质体上，与抗性癌细胞上的核仁素受体特异性结合。研究表明，脂质体在具有耐药性的荷瘤小鼠中具有长循环作用，靶向能力和显着的抗癌功效。这些研究进一步揭示了它们的作用机制，包括阻止微管解聚，阻止细胞周期，阻止JAK-STAT信号通路和抑制抗凋亡蛋白的活性。总之，功能性紫杉醇脂质体可用于有效治疗耐药性乳腺癌，并且这项研究还提供了一种基于核苷酸-脂质衍生物的新型靶向纳米药物。
更新日期：2021-04-01
中文翻译：
鸟嘌呤丰富的四链核苷酸脂质脂质修饰的功能性拉罗他赛脂质体的纳米结构，用于治疗抗性乳腺癌
乳腺癌是全世界女性中最常见的恶性疾病，其化疗结果受到多药耐药性的限制。在这里，开发了一种功能性拉罗他赛脂质体的纳米结构，该脂质体修饰有鸟嘌呤丰富的四链体核苷酸脂质衍生物，可用于治疗耐药性乳腺癌。该研究是针对耐药性乳腺癌细胞和荷瘤小鼠进行的。核苷酸-脂质衍生物（DSPE-PEG 2000 - C 6 - GT28nt）是通过在GT-28nt（包含17个鸟嘌呤和11个胸苷）和DSPE-PEG 2000之间引入疏水己基键合成的-NHS，并结合在功能性紫杉醇脂质体上，与抗性癌细胞上的核仁素受体特异性结合。研究表明，脂质体在具有耐药性的荷瘤小鼠中具有长循环作用，靶向能力和显着的抗癌功效。这些研究进一步揭示了它们的作用机制，包括阻止微管解聚，阻止细胞周期，阻止JAK-STAT信号通路和抑制抗凋亡蛋白的活性。总之，功能性紫杉醇脂质体可用于有效治疗耐药性乳腺癌，并且这项研究还提供了一种基于核苷酸-脂质衍生物的新型靶向纳米药物。
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