Abstract:
Antitumor agents often lack effective penetration and accumulation to achieve high therapeutic efficacy in treating solid tumors. Nanomotor-based nanomaterials offer a potential solution to address this obstacle. Among them, nitric oxide (NO) based nanomotors have garnered attention for their potential applications in nanomedicine. However, there widespread clinical adoption has been hindered by their complex preparation processes. To address this limitation, we have developed a NO-driven nanomotor utilizing a convenient and scalable nanogel preparation procedure. These nanomotors, loaded with the fluorescent probe / sonosensitizer chlorin e6 (Ce6), were specifically engineered for sonodynamic therapy. Through comprehensive in vitro investigations using both 2D and 3D cell models, as well as in vivo analysis of Ce6 fluorescent signal distribution in solid tumor models, we observed that the self-propulsion of these nanomotors significantly enhances cellular uptake and tumor penetration, particularly in solid tumors. This phenomenon enables efficient access to challenging tumor regions and, in some cases, results in complete tumor coverage. Notably, our nanomotors have demonstrated long-term in vivo biosafety. This study presents an effective approach to enhancing drug penetration and improving therapeutic efficacy in tumor treatment, with potential clinical relevance for future applications.
摘要:
抗肿瘤剂通常缺乏有效的渗透和积累以实现治疗实体瘤的高治疗功效。基于纳米马达的纳米材料提供了解决这一障碍的潜在解决方案。其中,基于一氧化氮(NO)的纳米马达因其在纳米医学中的潜在应用而受到关注。然而,其复杂的制备过程阻碍了广泛的临床采用。为了解决这个限制,我们已经开发了NO驱动的纳米电机,利用一个方便和可扩展的纳米凝胶制备程序。这些纳米马达,负载荧光探针/超声增敏剂二氢卟啉e6(Ce6),专门设计用于声动力疗法。通过使用2D和3D细胞模型进行全面的体外研究,以及在实体肿瘤模型中Ce6荧光信号分布的体内分析,我们观察到这些纳米马达的自我推进显着增强了细胞摄取和肿瘤渗透,特别是实体瘤。这种现象能够有效地进入具有挑战性的肿瘤区域,在某些情况下,结果完全覆盖肿瘤。值得注意的是,我们的纳米马达已经证明了长期的体内生物安全性。这项研究提出了一种有效的方法来增强药物渗透和提高肿瘤治疗的疗效,与未来应用的潜在临床相关性。