Aldea Mihaela, Potara Monica, Soritau Olga, Stefan Florian Ioan, Florea Adrian, Nagy-Simon Timea, Pileczki Valentina, Brie Ioana, Maniu Dana, Kacso Gabriel
Department of Medical Oncology and Radiotherapy, Iuliu Hatieganu University of Medicine and Pharmacy, Cluj-Napoca, Romania.
J BUON. 2018 May-Jun;23(3):800-813.
Glioblastoma is a rapidly evolving lethal disease mainly due to its highly chemo- and radioresistant glioblastoma stem cells (GSCs). Herein, we tested if chitosan-capped gold nanoparticles (Chit-GNPs) may overcome the limitations of drug concentrations by increased cell internalization in GSCs and if such GNPs could enhance the response to irradiation.
Chitosan was used for Chit-GNP synthesis as a reducing and stabilizing agent. Chit-GNPs were characterized by spectroscopy, dark field, transmission electron microscopy and zeta potential measurements. Patient-derived GSCs and human osteoblasts were treated with increasing concentrations of nanoparticles and irradiated. The uptake and cytotoxicity of Chit-GNPs were compared to that of uncoated GNPs.
The positively-charged, 26 nm-sized, spherical Chit-GNPs, showed a huge intracellular accumulation into the cytosol, lysosomes and near the nucleus, whereas no uncoated GNPs were internalized within GSCs. Surprisingly, Chit-GNPs were highly cytotoxic for GSCs irrespective of cell irradiation, that failed to add an additional benefit when combined with Chit-GNPs/GNPs. Moreover, Chit-GNPs were selectively cytotoxic for GSCs and did not affect the normal cells, despite an increased nanoparticle internalization.
The important Chit-GNP internalization and their selective cytotoxicity for GSCs make this compound a potential novel anticancer agent and a promising backbone for drug delivery in glioblastoma.
胶质母细胞瘤是一种快速发展的致命疾病，主要归因于其具有高度化学抗性和放射抗性的胶质母细胞瘤干细胞（GSCs）。在此，我们测试了壳聚糖包覆的金纳米颗粒（Chit-GNPs）是否可以通过增加在GSCs中的细胞内化来克服药物浓度的限制，以及这种纳米颗粒是否可以增强对辐射的反应。
使用壳聚糖作为还原剂和稳定剂来合成Chit-GNPs。通过光谱学、暗场、透射电子显微镜和zeta电位测量对Chit-GNPs进行表征。用不同浓度的纳米颗粒处理源自患者的GSCs和人成骨细胞并进行辐照。将Chit-GNPs的摄取和细胞毒性与未包覆的纳米颗粒进行比较。
带正电荷、尺寸为26nm的球形Chit-GNPs在细胞质、溶酶体和细胞核附近有大量细胞内积累，而GSCs内未摄取未包覆的纳米颗粒。令人惊讶的是，无论细胞是否接受辐照，Chit-GNPs对GSCs都具有高度细胞毒性，与Chit-GNPs/纳米颗粒联合使用时未显示出额外益处。此外，尽管纳米颗粒内化增加，但Chit-GNPs对GSCs具有选择性细胞毒性，且不影响正常细胞。
Chit-GNPs重要的细胞内化及其对GSCs的选择性细胞毒性使该化合物成为一种潜在的新型抗癌剂，也是胶质母细胞瘤药物递送的有前景的载体。
