Actively-targeted LTVSPWY peptide-modified magnetic nanoparticles for tumor imaging.
Actively-targeted LTVSPWY peptide-modified magnetic nanoparticles for tumor imaging.
复制标题
用于肿瘤成像的主动靶向 LTVSPWY 肽修饰磁性纳米颗粒。
DOI：
10.2147/ijn.s33593
复制
发表时间：
2012
影响因子：
8
通讯作者：
Du YZ
中科院分区：
文献类型：
--
作者：
Jie LY;Cai LL;Wang LJ;Ying XY;Yu RS;Zhang MM;Du YZ
磁共振成像（MRI）作为一种诊断工具被广泛应用于现代临床医学中，并且以高空间和时间分辨率提供活生物体中生物现象的非侵入性和三维可视化。因此，磁性纳米粒子作为MRI造影剂，具有高效的靶向性和细胞内化能力，能够提供更高的对比度和更丰富的图像信息，用于疾病的检测，受到了广泛的关注。采用化学反应法合成了LTVSPWY-PEG-CS（LTVSPWY-PEG-CS），并用1H-NMR对其结构进行了表征。采用溶剂扩散法成功制备了LTVSPWY-PEG-CS修饰的磁性纳米粒子。它们的粒径，粒径分布，和zeta电位进行了测量，通过动态光散射和电泳迁移率，并通过透射电子显微镜研究其表面形貌。为了研究它们的选择性靶向能力，在过表达HER 2的SKOV-3细胞和HER 2阴性的A549细胞的共培养系统中观察到LTVSPWY-PEG-CS修饰的磁性纳米颗粒的细胞摄取。采用MTT法测定纳米粒对SKOV-3和A549细胞的体外细胞毒性。采用SKOV-3荷瘤裸鼠模型研究磁性纳米粒子的体内靶向性。LTVSPWY-PEG-CS修饰的磁性纳米粒子的平均粒径为267.3 ± 23.4 nm，zeta电位为30.5 ± 7.0 mV，粒径分布较窄，呈球形。体外细胞毒性试验表明，这些磁性纳米粒子是适合用于癌症诊断的低毒性载体。通过对LTVSPWY归巢肽的修饰，当与HER 2阴性A549细胞共培养时，磁性纳米颗粒可以被过表达HER 2的SKOV-3细胞选择性地摄取。体内生物分布结果表明，用LTVSPWY-PEG-CS修饰的磁性纳米颗粒/DiR治疗能够在体内更快速有效地识别和诊断肿瘤。LTVSPWY-PEG-CS修饰的磁性纳米颗粒是一种有前途的造影剂，可用于早期检测过表达HER 2的肿瘤和进一步的诊断应用。
Magnetic resonance imaging (MRI) is widely used in modern clinical medicine as a diagnostic tool, and provides noninvasive and three-dimensional visualization of biological phenomena in living organisms with high spatial and temporal resolution. Therefore, considerable attention has been paid to magnetic nanoparticles as MRI contrast agents with efficient targeting ability and cellular internalization ability, which make it possible to offer higher contrast and information-rich images for detection of disease. LTVSPWY peptide-modified PEGylated chitosan (LTVSPWY-PEG-CS) was synthesized by chemical reaction, and the chemical structure was confirmed by 1H-NMR. LTVSPWY-PEG-CS-modified magnetic nanoparticles were prepared successfully using the solvent diffusion method. Their particle size, size distribution, and zeta potential were measured by dynamic light scattering and electrophoretic mobility, and their surface morphology was investigated by transmission electron microscopy. To investigate their selective targeting ability, the cellular uptake of the LTVSPWY-PEG-CS-modified magnetic nanoparticles was observed in a cocultured system of SKOV-3 cells which overexpress HER2 and A549 cells which are HER2-negative. The in vitro cytotoxicity of these nanoparticles in SKOV-3 and A549 cells was measured using the MTT method. The SKOV-3-bearing nude mouse model was used to investigate the tumor targeting ability of the magnetic nanoparticles in vivo. The average diameter and zeta potential of the LTVSPWY-PEG-CS-modified magnetic nanoparticles was 267.3 ± 23.4 nm and 30.5 ± 7.0 mV, respectively, with a narrow size distribution and spherical morphology. In vitro cytotoxicity tests demonstrated that these magnetic nanoparticles were carriers suitable for use in cancer diagnostics with low toxicity. With modification of the LTVSPWY homing peptide, magnetic nanoparticles could be selectively taken up by SKOV-3 cells overexpressing HER2 when cocultured with HER2-negative A549 cells. In vivo biodistribution results suggest that treatment with LTVSPWY-PEG-CS-modified magnetic nanoparticles/DiR enabled tumors to be identified and diagnosed more rapidly and efficiently in vivo. LTVSPWY-PEG-CS-modified magnetic nanoparticles are a promising contrast agent for early detection of tumors overexpressing HER2 and further diagnostic application.