Construction and Evaluation of a Targeted Hyaluronic Acid Nanoparticle/Photosensitizer Complex for Cancer Photodynamic Therapy
Construction and Evaluation of a Targeted Hyaluronic Acid Nanoparticle/Photosensitizer Complex for Cancer Photodynamic Therapy
复制标题
用于癌症光动力治疗的靶向透明质酸纳米颗粒/光敏剂复合物的构建和评估。
DOI：
10.1021/acsami.7b09331
复制
发表时间：
2017-09-27
影响因子：
9.5
通讯作者：
Zhu, Lei
中科院分区：
文献类型：
--
作者：
Gao, Shi;Wang, Jingjing;Zhu, Lei
光动力疗法（PDT）是一种新型的治疗方式，正在对包括癌症在内的各种疾病进行深入的临床前研究。尽管在这一领域进行了广泛的研究，但可以特异性地在肿瘤中积累以达到治疗浓度的选择性和有效的光动力剂是有限的。虽然最近的尝试已经产生了与各种纳米材料复合的光敏剂（PS），但繁琐的制备步骤和较差的肿瘤治疗效率阻碍了它们的利用。在这里，我们通过将光敏剂Ce 6物理封装到透明质酸纳米颗粒（HANP）中来开发了一种靶向CD 44的纳米光动力剂，其在此表示为HANP/Ce 6。在体外和体内对其物理特性和光动力学治疗能力进行了表征。HANP/Ce 6的全身递送导致其在人结肠癌异种移植模型中的积累。肿瘤/肌肉比在注射后4小时达到3.47 ± 0.46，如通过荧光成像证实的。与肿瘤对照组相比，用激光照射（0.15 W/cm 2，630 nm）的HANP/Ce 6处理后的肿瘤生长显著抑制9.61 ± 1.09倍，肿瘤对照组显示肿瘤生长无变化。未观察到对小鼠的明显全身和局部毒性作用。HANP/Ce 6介导的肿瘤生长抑制在治疗后1天通过18F-fluoro-2-deoxy-d-glucose正电子发射断层扫描首次进行评估和观察，并在我们的治疗时间窗内持续14天。总之，我们的结果突出了新型HANP/Ce 6治疗诊断纳米颗粒用于CD 44靶向PDT癌症治疗的成像特性和治疗效果，其可能在临床中潜在地使用。该HANP系统也可用于递送其他疏水PS，特别是那些不能被化学修饰的疏水PS。
Photodynamic therapy (PDT) is a novel treatment modality that is under intensive preclinical investigations for a variety of diseases, including cancer. Despite extensive studies in this area, selective and effective photodynamic agents that can specifically accumulate in tumors to reach a therapeutic concentration are limited. Although recent attempts have produced photosensitizers (PSs) complexed with various nanomaterials, the tedious preparation steps and poor tumor efficiency of therapy hamper their utilization. Here, we developed a CD44-targeted nanophotodynamic agent by physically encapsulating a photosensitizer, Ce6, into a hyaluronic acid nanoparticle (HANP), which was hereby denoted HANP/Ce6. Its physical features and capability for photodynamic therapy were characterized in vitro and in vivo. Systemic delivery of HANP/Ce6 resulted in its accumulation in a human colon cancer xenograft model. The tumor/muscle ratio reached 3.47 ± 0.46 at 4 h post injection, as confirmed by fluorescence imaging. Tumor growth after HANP/Ce6 treatment with laser irradiation (0.15 W/cm2, 630 nm) was significantly inhibited by 9.61 ± 1.09-fold compared to that in tumor control groups, which showed no change in tumor growth. No apparent systemic and local toxic effects on the mice were observed. HANP/Ce6-mediated tumor growth inhibition was accessed and observed for the first time by 18F-fluoro-2-deoxy-d-glucose positron emission tomography as early as 1 day after treatment and persisted for 14 days within our treatment time window. In sum, our results highlight the imaging properties and therapeutic effects of the novel HANP/Ce6 theranostic nanoparticle for CD44-targeted PDT cancer therapy that may be potentially utilized in the clinic. This HANP system may also be applied for the delivery of other hydrophobic PSs, particularly those that could not be chemically modified.