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Janus rod-like micromotors to promote the tumor accumulation and cell internalization of therapeutic agents
Chemical Engineering Journal ( IF 13.3 ) Pub Date : 2020-09-22 , DOI: 10.1016/j.cej.2020.127073
Zhanlin Zhang , Hui Yan , Shang Li , Yuan Liu , Pan Ran , Weijia Chen , Xiaohong Li

The navigation of drug-loaded nanocarriers is confronted with series of physiological and pathological barriers in blood circulation, tissue penetration and cell internalization. In the current study, self-propelled micromotors of fiber rods are proposed to address the transportation barriers of chemotherapeutic drugs. Fiber rods with distinct Janus structure are prepared by side-by-side electrospinning, and urease and folate are conjugated on the respective sides of Janus rods (JRs) as power source and targeting ligands of Janus micromotors (JMs). The grafting density of urease determines the motion velocity and trajectory of JMs, and the high motion velocity and large mean-square displacement are detected in both phosphate-buffered saline and simulated extracellular matrices of tumor tissues. Despite no interference with the uptake pathway, the self-propelled motion promotes the folate-mediated cell internalization of JMs and maximizes the toxicities and apoptosis rate of tumor cells. The self-propulsion force from one side of JMs enhances the lateral drift and extravasation across blood vessel walls, increasing their accumulation in tumor tissues by around 2 folds and, doxorubicin accumulation, by around 2.6 folds. The treatment with JMs remarkably inhibits the tumor growth, prolongs the animal survival rate and induces strong tumor necrosis without obvious histopathological and hematological abnormalities to normal tissues. Thus, this study demonstrates a feasible strategy in combating the navigation barriers of blood vessel extravasation, tumor tissue diffusion and cell capture, effectively promoting the treatment efficacy and alleviating side effects of chemotherapeutic agents.



中文翻译:

Janus棒状微电机,促进肿瘤蓄积和细胞内在化治疗剂

载有药物的纳米载体的导航在血液循环,组织渗透和细胞内化方面面临一系列生理和病理障碍。在当前的研究中,提出了纤维棒自走式微型电动机,以解决化学治疗药物的运输障碍。通过并排静电纺丝制备具有截然不同的Janus结构的纤维棒,并将尿素酶和叶酸共轭在Janus棒(JRs)的两侧,作为Janus微电机(JMs)的动力源和靶向配体。脲酶的接枝密度决定了JMs的运动速度和轨迹,在磷酸盐缓冲液和肿瘤组织的模拟细胞外基质中均检测到高运动速度和较大的均方位移。尽管不影响摄取途径,自推进运动促进叶酸介导的JMs细胞内在化并最大化肿瘤细胞的毒性和细胞凋亡率。JMs一侧的自推力增强了血管壁的侧向漂移和外渗,使它们在肿瘤组织中的积聚增加了约2倍,而阿霉素的积聚则增加了约2.6倍。JMs的治疗显着抑制了肿瘤的生长,延长了动物的存活率并诱导了强烈的肿瘤坏死,而对正常组织没有明显的组织病理学和血液学异常。因此,该研究证明了在对抗血管外渗,肿瘤组织扩散和细胞捕获的导航障碍,有效地提高治疗功效和减轻化学治疗剂的副作用方面的可行策略。

更新日期:2020-09-22
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