Scalable fabrication of metal-phenolic nanoparticles by coordination-driven flash nanocomplexation for cancer theranostics
Scalable fabrication of metal-phenolic nanoparticles by coordination-driven flash nanocomplexation for cancer theranostics
复制标题
通过配位驱动的闪光纳米络合可扩展地制造金属酚类纳米粒子，用于癌症治疗诊断
DOI：
10.1039/c9nr02185j
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发表时间：
2019-05-21
期刊：
影响因子：
6.7
通讯作者：
Chen, Yongming
中科院分区：
文献类型：
--
作者：
Liu, Zhijia;Le, Zhicheng;Chen, Yongming
尽管已经开发了各种纳米材料用于癌症治疗诊断，但通过简单且可扩展的方法将治疗药物和诊断剂有效整合到单个多组分纳米颗粒中仍然存在关键挑战。此外，目前纳米制剂在组成可控性、胶体稳定性、载药能力和批次间重复性方面的瓶颈仍然阻碍着纳米医学的临床转化。在此，我们报告了一种配位驱动的闪光纳米络合（cFNC）过程，通过在快速湍流混合中有效控制配位反应动力学，实现了具有透明质酸表面层的多柔比星基金属-酚醛纳米颗粒（DITH）的可扩展制造。优化后的DITH具有较小的流体动力学直径（84 nm）、较窄的粒径分布、较高的载药量（26.6%）、较高的重现性和pH触发的药物释放行为。研究表明，由于DITH对环境pH刺激的敏感性，DITH显著增加了由CD 44（+）受体靶向介导的细胞内吞作用，并加速了细胞内药物释放。此外，在铁离子赋予的T-1加权磁共振（MR）成像功能的指导下，DITH在MCF-7荷瘤小鼠模型中静脉注射后表现出延长血液循环，增强肿瘤蓄积，改善治疗性能并降低毒副作用。这些结果证实了所开发的DITH是一种有前途的癌症治疗诊断应用工具，我们的工作为促进翻译纳米医学的发展提供了一种新的策略。
Although various nanomaterials have been developed for cancer theranostics, there remains a key challenge for effective integration of therapeutic drugs and diagnostic agents into a single multicomponent nanoparticle via a simple and scalable approach. Moreover, the bottlenecks of nanoformulation in composition controllability, colloidal stability, drug loading capability and batch-to-batch repeatability currently still hinder the clinical translation of nanomedicine. Herein, we report a coordination-driven flash nanocomplexation (cFNC) process to achieve scalable fabrication of doxorubicin-based metal-phenolic nanoparticles (DITH) with a hyaluronic acid surface layer through efficient control of coordination reaction kinetics in a rapid turbulent mixing. The optimized DITH exhibited a small hydrodynamic diameter (84 nm), narrow size distribution, high drug loading capacity (26.6%), high reproducibility and pH-triggered drug release behaviors. The studies indicated that DITH significantly increased cellular endocytosis mediated by CD44(+) receptor targeting and accelerated intracellular drug release owing to the sensitivity of DITH to environmental pH stimuli. Furthermore, guided by T-1-weighted magnetic resonance (MR) imaging function endowed by ferric ions, DITH exhibited prolonged blood circulation, enhanced tumor accumulation, improved therapeutic performance and decreased toxic side effects after intravenous injection in a MCF-7 tumor-bearing mice model. These results confirmed that the developed DITH is a promising vehicle for cancer theranostic applications, and our work provided a new strategy to promote the development of translational nanomedicine.