School of Pharmaceutical Sciences, Wenzhou Medical University, Wenzhou City, Zhejiang Province 325035, China.
Nanoscale. 2016 Aug 7;8(29):14222-36. doi: 10.1039/c6nr02448c. Epub 2016 Jul 11.
Multifunctional nanoparticles capable of the specific delivery of therapeutics to diseased cells and the real-time imaging of these sites have the potential to improve cancer treatment through personalized therapy. In this study, we have proposed a multifunctional nanoparticle that integrate magnetic targeting, drug-carrier functionality and real-time MRI imaging capabilities in one platform for the theranostic treatment of tumors. The multifunctional nanoparticle was designed with a superparamagnetic iron oxide core and a multifunctional shell composed of PEG/PEI/polysorbate 80 (Ps 80) and was used to encapsulate DOX. DOX-loaded multifunctional nanoparticles (DOX@Ps 80-SPIONs) with a Dh of 58.0 nm, a zeta potential of 28.0 mV, and a drug loading content of 29.3% presented superior superparamagnetic properties with a saturation magnetization (Ms) of 24.1 emu g(-1). The cellular uptake of DOX@Ps 80-SPIONs by C6 cells under a magnetic field was significantly enhanced over that of free DOX in solution, resulting in stronger in vitro cytotoxicity. The real-time therapeutic outcome of DOX@Ps 80-SPIONs was easily monitored by MRI. Furthermore, the negative contrast enhancement effect of the nanoparticles was confirmed in glioma-bearing rats. Prussian blue staining and ex vivo DOX fluorescence assays showed that the magnetic Ps 80-SPIONs and encapsulated DOX were delivered to gliomas by imposing external magnetic fields, indicating effective magnetic targeting. Due to magnetic targeting and Ps 80-mediated endocytosis, DOX@Ps 80-SPIONs in the presence of a magnetic field led to the complete suppression of glioma growth in vivo at 28 days after treatment. The therapeutic mechanism of DOX@Ps 80-SPIONs acted by inducing apoptosis through the caspase-3 pathway. Finally, DOX@Ps 80-SPIONs' safety at therapeutic dosage was verified using pathological HE assays of the heart, liver, spleen, lung and kidney. Multifunctional SPIONs could be used as potential carriers for the theranostic treatment of CNS diseases.
多功能纳米颗粒能够将治疗药物特异性递送至病变细胞，并实时成像这些部位，有可能通过个性化治疗改善癌症治疗效果。在这项研究中，我们提出了一种多功能纳米颗粒，它将磁靶向、药物载体功能和实时 MRI 成像能力集成在一个平台上，用于肿瘤的治疗诊断。该多功能纳米颗粒设计有超顺磁氧化铁核心和多功能外壳，由聚乙二醇/聚乙烯亚胺/聚山梨酯 80（Ps 80）和多糖 80 组成，并用于封装 DOX。载 DOX 的多功能纳米颗粒（DOX@Ps 80-SPIONs）的 Dh 为 58.0nm，zeta 电位为 28.0mV，药物载量为 29.3%，具有优越的超顺磁性，饱和磁化强度（Ms）为 24.1emu g(-1)。在磁场下，C6 细胞对 DOX@Ps 80-SPIONs 的摄取明显高于游离 DOX 在溶液中的摄取，导致体外细胞毒性更强。通过 MRI 很容易监测到 DOX@Ps 80-SPIONs 的实时治疗效果。此外，在荷瘤大鼠中证实了纳米颗粒的负对比增强效应。普鲁士蓝染色和离体 DOX 荧光分析表明，通过施加外部磁场，磁性 Ps 80-SPIONs 和包裹的 DOX 被递送至脑肿瘤，表明具有有效的磁靶向作用。由于磁靶向和 Ps 80 介导的内吞作用，在磁场存在下，DOX@Ps 80-SPIONs 在治疗后 28 天导致体内胶质瘤完全抑制。DOX@Ps 80-SPIONs 的治疗机制通过 caspase-3 途径诱导细胞凋亡。最后，通过心脏、肝脏、脾脏、肺和肾脏的病理 HE 分析验证了治疗剂量下 DOX@Ps 80-SPIONs 的安全性。多功能 SPIONs 可作为 CNS 疾病治疗诊断的潜在载体。
