State Key Laboratory of Bioelectronics, Jiangsu Key Laboratory for Biomaterials and Devices, School of Biological Science and Medical Engineering & Collaborative Innovation Center of Suzhou Nano-Science and Technology, Suzhou Key Laboratory of Biomaterials and Technologies , Southeast University , Nanjing 210096 , P.R. China.
Department of Pharmaceutics , China Pharmaceutical University , Nanjing 210009 , P.R. China.
ACS Appl Mater Interfaces. 2019 Aug 21;11(33):29536-29548. doi: 10.1021/acsami.9b08948. Epub 2019 Aug 6.
Previous reports from our team revealed the significant potential advantage of Mn-Zn ferrite nanoparticles (NPs) in magnetic resonance imaging (MRI), whereas anisotropic NPs reportedly increased the blood circulation time of nanocarriers. Thus, anisotropic Mn-Zn ferrite displayed a huge potential in cancer synchronous diagnosis and treatment, that is, enhanced MRI observation was performed simultaneously when drug-targeted delivery therapy was applied to the tumor. Here, we developed three shaped Mn-Zn ferrite (MnZnFeO) MNPs used as cancer theranostic nanoagents and compared the effect of the three shaped MNPs on cancer theranostics. Compared to the monodisperse sphere MNPs (S-MNPs-PPR) and clustering MNPs (C-MNPs-PPR), worm-like Mn-Zn ferrite MNPs (W-MNPs-PPR) achieved better results in -weighted MRI and achieved more sustained drug release than S-MNPs-PPR and more complete drug release than C-MNPs-PPR in vitro. Additionally, polyethylene glycol (PEG) coating and RGD modification encouraged the three shaped MNPs to evade the recruitment of macrophages more easily and to target the integrin-enriched endothelial cells instead. Meanwhile, W-MNPs-PPR coupled with Paclitaxel (PTX) exhibited more delivery of PTX in the integrin-enriched cells than the other two shaped MNPs, and the content of PTX was far more than that of the wild-type Taxol control group. What is more, in vivo results demonstrated that PTX-coated W-MNPs-PPR not only gained good dual-mode imaging in the tumor (MRI and fluorescence images) but also achieved longer blood circulation time and more PTX-targeted delivery to the tumor, as well as more efficiency in tumor cell killing, which make the simultaneous diagnosis and treatment of tumors to be conducted. Therefore, our works further revealed the importance of the NP shape on its functionality and ultimately provided an alternative and efficient worm-like theranostic nanoagent for tumor theranostics.
先前，我们团队的报告揭示了 Mn-Zn 铁氧体纳米粒子（NPs）在磁共振成像（MRI）方面的巨大优势，而各向异性 NPs 据报道可增加纳米载体的血液循环时间。因此，各向异性 Mn-Zn 铁氧体在癌症同步诊断和治疗方面具有巨大的潜力，即在将靶向药物输送疗法应用于肿瘤的同时，进行增强的 MRI 观察。在这里，我们开发了三种形状的 Mn-Zn 铁氧体（MnZnFeO）MNPs 作为癌症治疗诊断纳米制剂，并比较了这三种形状的 MNPs 对癌症治疗诊断的影响。与单分散球体 MNPs（S-MNPs-PPR）和聚集体 MNPs（C-MNPs-PPR）相比，蠕虫状 Mn-Zn 铁氧体 MNPs（W-MNPs-PPR）在 -加权 MRI 中表现出更好的效果，并且在体外比 S-MNPs-PPR 具有更持续的药物释放，并且比 C-MNPs-PPR 更完全的药物释放。此外，聚乙二醇（PEG）涂层和 RGD 修饰鼓励这三种形状的 MNPs 更容易逃避巨噬细胞的募集，转而靶向富含整合素的内皮细胞。同时，W-MNPs-PPR 与紫杉醇（PTX）结合后，在富含整合素的细胞中输送的 PTX 比其他两种形状的 MNPs 更多，并且 PTX 的含量远远超过野生型紫杉醇对照组。更重要的是，体内结果表明，PTX 涂层的 W-MNPs-PPR 不仅在肿瘤（MRI 和荧光图像）中获得了良好的双模成像，而且还延长了血液循环时间，并更有效地将 PTX 靶向递送至肿瘤，以及更有效地杀死肿瘤细胞，从而实现了肿瘤的同时诊断和治疗。因此，我们的工作进一步揭示了 NP 形状对其功能的重要性，并最终为肿瘤治疗诊断提供了一种替代的、高效的蠕虫状治疗诊断纳米制剂。
