Department of Biomedical Engineering, McGill University, 3775 University Street, Montreal QC, H3A 2B4, Canada.
Nanotechnology. 2012 Jul 11;23(27):275103. doi: 10.1088/0957-4484/23/27/275103. Epub 2012 Jun 19.
Direct comparisons of different types of nanoparticles for drug delivery have seldom been performed. In this study we compare the physical properties and cellular activity of doxorubicin (Dox) conjugates to gold nanoparticles (Au) and InP quantum dots of comparable diameter. Although the Au particles alone are non-toxic and InP is moderately toxic, Au-Dox is more effective than InP-Dox against the Dox-resistant B16 melanoma cell line. Light exposure does not augment the efficacy of InP-Dox, suggesting that conjugates are breaking down. Electron and confocal microscopy and atomic absorption spectroscopy reveal that over 60% of the Au-Dox conjugates reach the cell nucleus. In contrast, InP-Dox enters cell nuclei to a very limited extent, although liberated Dox from the conjugates does eventually reach the nucleus. These observations are attributed to faster Dox release from Au conjugates under endosomal conditions, greater aggregation of InP-Dox with cytoplasmic proteins, and adherence of InP to membranes. These findings have important implications for design of active drug-nanoparticle conjugates.
直接比较不同类型的纳米颗粒用于药物输送的情况很少见。在这项研究中，我们比较了阿霉素（Dox）缀合物与金纳米颗粒（Au）和具有相似直径的 InP 量子点的物理性质和细胞活性。尽管单独的 Au 颗粒本身是无毒的，InP 是中度有毒的，但 Au-Dox 对多柔比星耐药的 B16 黑色素瘤细胞系的疗效优于 InP-Dox。光照并不能增强 InP-Dox 的疗效，这表明缀合物正在分解。电子和共聚焦显微镜以及原子吸收光谱显示，超过 60%的 Au-Dox 缀合物到达细胞核。相比之下，InP-Dox 进入细胞核的程度非常有限，尽管从缀合物中释放的游离 Dox 最终会到达细胞核。这些观察结果归因于在内涵体条件下 Au 缀合物中 Dox 的更快释放、InP-Dox 与细胞质蛋白的更大聚集以及 InP 与膜的粘附。这些发现对设计活性药物-纳米颗粒缀合物具有重要意义。
