Polymer Science Department , Iran Polymer & Petrochemical Institute , P.O. Box 14965/115, Tehran 1497713115 , Iran.
Medical Physics Department, School of Medicine , Iran University of Medical Sciences , Tehran 1449614525 , Iran.
ACS Appl Mater Interfaces. 2018 Jun 13;10(23):19483-19493. doi: 10.1021/acsami.8b05252. Epub 2018 May 30.
Tumor-selective photodynamic therapy is a successful method for ablation of malignant and cancerous cells. Herein, we introduce the design and preparation of functionalized acrylic copolymer nanoparticles with spiropyran (SP) and imidazole groups through a facile semicontinuous emulsion polymerization. Then, Au ions were immobilized and reduced on their surface to obtain photoresponsive gold-decorated polymer nanoparticles (PGPNPs). The prepared PGPNPs were surface-modified with folic acid as a site-specific tumor cell targeting agent and improve intracellular uptake via endocytosis. Fourier transform infrared spectroscopy and energy dispersive X-ray spectroscopy analyses, UV-vis spectroscopy, scanning electron microscopy, and high-resolution transmission electron microscopy images were employed to characterize their spectral and morphological properties. Fluorescence microscopy images and inductively coupled plasma analysis demonstrated the cell line labeling capability and improved targeting efficiency of folate-conjugated PGPNPs (FA-PGPNPs) toward rat brain cancer cells (C6 glioma) with 71.8% cell uptake in comparison with 28.8% for the nonconjugated ones. Nonpolar SP groups are converted to zwitterionic merocyanine isomers under UV irradiation at 365 nm and their conjugation with Au nanoparticles exhibited enhanced photogeneration of reactive oxygen species (ROS). These were confirmed by intracellular ROS analysis and cytotoxicity evaluation on malignant C6 glioma cells. Owing to the strong surface plasmon resonance absorption of gold nanoparticles, FA-PGPNPs provided elevated local photothermal efficiency under near-IR irradiation at 808 nm. The prepared multifunctional FA-PGPNPs with a comprehensive integration of prospective materials introduced promising nanoprobes with targeting ability, enhanced tumor photodynamic therapy, cell tracking, and photothermal therapy.
肿瘤选择性光动力疗法是一种成功的方法，用于消融恶性和癌细胞。在此，我们通过简便的半连续乳液聚合方法，介绍了具有螺吡喃（SP）和咪唑基团的功能化丙烯酸共聚物纳米粒子的设计和制备。然后，将 Au 离子固定并还原在其表面上，以获得光响应的金修饰聚合物纳米粒子（PGPNPs）。制备的 PGPNPs 表面用叶酸进行了修饰，作为一种特异性肿瘤细胞靶向剂，并通过内吞作用提高细胞内摄取。傅里叶变换红外光谱和能谱分析、紫外可见光谱、扫描电子显微镜和高分辨率透射电子显微镜图像用于表征其光谱和形态特性。荧光显微镜图像和电感耦合等离子体分析表明，叶酸偶联的 PGPNPs（FA-PGPNPs）具有细胞系标记能力，对大鼠脑癌细胞（C6 神经胶质瘤）的靶向效率提高了 71.8%，而未偶联的 PGPNPs 的靶向效率为 28.8%。非极性 SP 基团在 365nm 的紫外光照射下转化为两性离子的次甲蓝异构体，其与 Au 纳米粒子的结合表现出增强的活性氧（ROS）的光生成。通过细胞内 ROS 分析和对恶性 C6 神经胶质瘤细胞的细胞毒性评估证实了这一点。由于金纳米粒子的强表面等离子体共振吸收，FA-PGPNPs 在 808nm 的近红外照射下提供了更高的局部光热效率。所制备的具有多功能的 FA-PGPNPs 综合了引入的有前途的材料，具有靶向能力、增强的肿瘤光动力疗法、细胞跟踪和光热疗法。
