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Cancer Cell Preferential Penetration and pH-Responsive Drug Delivery of Oligorutin
Biomacromolecules ( IF 6.2 ) Pub Date : 2021-08-12 , DOI: 10.1021/acs.biomac.1c00268 Weiying Hong 1 , Chang-Cheng Liu 1 , Henan Zhang 1 , Zhiyong Chen 2 , Min Xiao 3 , Li Xu 1
Biomacromolecules ( IF 6.2 ) Pub Date : 2021-08-12 , DOI: 10.1021/acs.biomac.1c00268 Weiying Hong 1 , Chang-Cheng Liu 1 , Henan Zhang 1 , Zhiyong Chen 2 , Min Xiao 3 , Li Xu 1
Affiliation
We report herein a novel delivery system, derived from the facile enzymatic synthesis of oligorutin (OR), for cancer cell targeting and pH-responsive drug delivery. In this study, we demonstrate that OR could preferentially penetrate cancer cells via the lipid raft-mediated endocytosis pathway, and cell membrane cholesterol was critical to the internalization of OR. The accumulation of OR in the tumor region was further confirmed by an in vivo biodistribution study. Considering the tumor-targeting property of OR, a pH-responsive drug delivery system (OR–BTZ) was developed by covalent conjugation of the catechol groups on OR with antitumor drug bortezomib (BTZ) through a pH-sensitive borate ester bond. OR–BTZ exerted cytotoxicity as well as inhibition of the migration and invasion to hepatoma carcinoma cells and showed no apparent cytotoxicity with liver normal cells. The OR–BTZs also presented significant therapeutic efficacy and low systematic toxicity in the murine hepatocellular carcinoma model. To our knowledge, this study presents the first attempt to exploit the potential of oligoflavonoids for cancer cell-targeted drug delivery and will motivate the development of flavonoids and their derivatives as a new type of biomaterials for tumor-targeted therapy.
中文翻译:
Oligorutin 的癌细胞优先渗透和 pH 响应药物递送
我们在此报告了一种新的递送系统,该系统源自低聚糖 (OR) 的简便酶促合成,用于癌细胞靶向和 pH 响应性药物递送。在这项研究中,我们证明 OR 可以通过脂筏介导的内吞途径优先穿透癌细胞,细胞膜胆固醇对 OR 的内化至关重要。体内生物分布研究进一步证实了 OR 在肿瘤区域的积累。考虑到 OR 的肿瘤靶向特性,通过 pH 敏感的硼酸酯键将 OR 上的儿茶酚基团与抗肿瘤药物硼替佐米 (BTZ) 共价结合,开发了 pH 响应性药物递送系统 (OR-BTZ)。OR-BTZ对肝癌细胞具有细胞毒性以及抑制迁移和侵袭的作用,对肝正常细胞没有明显的细胞毒性。OR-BTZ 在鼠肝细胞癌模型中也表现出显着的治疗效果和低系统毒性。据我们所知,这项研究首次尝试利用寡黄酮类化合物在癌细胞靶向药物递送方面的潜力,并将推动类黄酮类化合物及其衍生物作为一种新型生物材料用于肿瘤靶向治疗的发展。
更新日期:2021-09-13
中文翻译:
Oligorutin 的癌细胞优先渗透和 pH 响应药物递送
我们在此报告了一种新的递送系统,该系统源自低聚糖 (OR) 的简便酶促合成,用于癌细胞靶向和 pH 响应性药物递送。在这项研究中,我们证明 OR 可以通过脂筏介导的内吞途径优先穿透癌细胞,细胞膜胆固醇对 OR 的内化至关重要。体内生物分布研究进一步证实了 OR 在肿瘤区域的积累。考虑到 OR 的肿瘤靶向特性,通过 pH 敏感的硼酸酯键将 OR 上的儿茶酚基团与抗肿瘤药物硼替佐米 (BTZ) 共价结合,开发了 pH 响应性药物递送系统 (OR-BTZ)。OR-BTZ对肝癌细胞具有细胞毒性以及抑制迁移和侵袭的作用,对肝正常细胞没有明显的细胞毒性。OR-BTZ 在鼠肝细胞癌模型中也表现出显着的治疗效果和低系统毒性。据我们所知,这项研究首次尝试利用寡黄酮类化合物在癌细胞靶向药物递送方面的潜力,并将推动类黄酮类化合物及其衍生物作为一种新型生物材料用于肿瘤靶向治疗的发展。