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Trojan-Horse Diameter-Reducible Nanotheranostics for Macroscopic/Microscopic Imaging-Monitored Chemo-Antiangiogenic Therapy
ACS Applied Materials & Interfaces ( IF 8.3 ) Pub Date : 2022-01-19 , DOI: 10.1021/acsami.1c22350
Zhongxiong Fan 1 , Dao Shi 1 , Wenbao Zuo 2 , Juan Feng 3 , Dongtao Ge 1 , Guanghao Su 4 , Lichao Yang 5 , Zhenqing Hou 1
Affiliation  

Although nanotheranostics have displayed striking potential toward precise nanomedicine, their targeting delivery and tumor penetration capacities are still impeded by several biological barriers. Besides, the current antitumor strategies mainly focus on killing tumor cells rather than antiangiogenesis. Enlightened by the fact that the smart transformable self-targeting nanotheranostics can enhance their targeting efficiency, tumor penetration, and cellular uptake, we herein report carrier-free Trojan-horse diameter-reducible metal–organic nanotheranostics by the coordination-driven supramolecular sequential co-assembly of the chemo-drug pemetrexed (PEM), transition-metal ions (FeIII), and antiangiogenesis pseudolaric acid B. Such nanotheranostics with both a high dual-drug payload efficiency and outstanding physiological stability are responsively decomposed into numerous ultra-small-diameter nanotheranostics under stimuli of the moderate acidic tumor microenvironment and then internalized into tumor cells through tumor-receptor-mediated self-targeting, synergistically enhancing tumor penetration and cellular uptake. Besides, such nanotheranostics enable visualization of self-targeting capacity under the macroscopic monitor of computed tomography/magnetic resonance imaging, thereby realizing efficient oncotherapy. Moreover, tumor microvessels are precisely monitored by optical coherence tomography angiography/laser speckle imaging during chemo-antiangiogenic therapy in vivo, visually verifying that such nanotheranostics possess an excellent antiangiogenic effect. Our work will provide a promising strategy for further tumor diagnosis and targeted therapy.

中文翻译:

Trojan-Horse Diameter-reducible Nanotheranostics 用于宏观/显微成像监测的化学抗血管生成治疗

尽管纳米治疗学在精确纳米医学方面显示出惊人的潜力,但它们的靶向递送和肿瘤穿透能力仍然受到一些生物障碍的阻碍。此外,目前的抗肿瘤策略主要集中在杀死肿瘤细胞而不是抗血管生成。受智能可转换自靶向纳米治疗可以提高其靶向效率、肿瘤穿透和细胞摄取这一事实的启发,我们在此报告了通过配位驱动的超分子顺序共-化学药物培美曲塞 (PEM)、过渡金属离子 (Fe III) 和抗血管生成假月桂酸 B。这种兼具高双药有效载荷效率和出色生理稳定性的纳米治疗药物在中度酸性肿瘤微环境的刺激下响应性分解成众多超小直径纳米治疗药物,然后通过肿瘤内化到肿瘤细胞中。 -受体介导的自我靶向,协同增强肿瘤穿透和细胞摄取。此外,这种纳米治疗可以在计算机断层扫描/磁共振成像的宏观监测下可视化自我靶向能力,从而实现高效的肿瘤治疗。此外,在体内化学抗血管生成治疗期间,通过光学相干断层扫描血管造影/激光散斑成像精确监测肿瘤微血管,视觉验证这种纳米治疗药物具有优异的抗血管生成作用。我们的工作将为进一步的肿瘤诊断和靶向治疗提供有前景的策略。
更新日期:2022-02-02
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