Abstract

Zinc oxide (ZnO) nanoparticles, due to their well-defined physico-chemical and antimicrobial attributes have been presented lately as favourable theranostic nanoplatforms for drug delivery. We hypothesized that surface modification of ZnO nanoparticle with activated polyethylene glycol and folic acid might be of great importance in targeted drug delivery in nasopharyngeal carcinoma since carcinoma cells possess folate receptors absent in normal cells. Therefore in this study, we have prepared and characterized activated PEG and folate conjugated dual drug loaded ZnO nanoparticles for increased cellular uptake efficiency in nasopharyngeal cancer cell lines. We synthesized the ZnO nanoparticles using sol-gel technique, conjugated them with activated PEG and folate and loaded them with two conventional anti-cancer drugs, namely cisplatin and docetaxel. The nanoparticle formulations were characterized by electron microscopy, stability studies, in-vitro release studies(acidic and normal pH), encapsulation & loading efficiency studies, FTIR and cytotoxicity studies. Additionally, cellline studies were done to assess cellular uptake efficiency using HNE-1 and CNE-2 cells. The dual drug loaded, folate & PEG activated ZnO nanoparticle were found to be extremely small size with high zeta potential & polydispersity index and high entrapment efficiency (82%) too. The nanoparticle formulations had stability and did not aggregate when kept in dispersed form for a long time. Moreover, they were found to be cytocompatible with negligible side-effects when incubated with normal cells. They also exhibited higher cellular uptake efficiencies when compared with free form. Therefore, it may safely concluded that combinatorial drug loaded, folate & PEG activated ZnO nanoparticle may result in better uptake of chemotherapeutic drugs with lower toxicity to normal cells.

摘要

氧化锌（ZnO）纳米颗粒由于其定义明确的物理化学和抗菌特性，最近被作为药物递送的治疗性纳米平台被提出。我们假设用活化的聚乙二醇和叶酸对ZnO纳米颗粒进行表面修饰可能在鼻咽癌靶向给药中非常重要，因为癌细胞具有正常细胞中不存在的叶酸受体。因此，在这项研究中，我们已经制备并表征了活化的PEG和叶酸偶联的双重药物负载ZnO纳米颗粒，以提高鼻咽癌细胞系的细胞摄取效率。我们使用溶胶-凝胶技术合成了ZnO纳米颗粒，将其与活化的PEG和叶酸偶联，并在其中装载了两种常规的抗癌药物，即顺铂和多西他赛。通过电子显微镜，稳定性研究，体外释放研究（酸性和正常pH），封装和负载效率研究，FTIR和细胞毒性研究。另外，进行了细胞系研究以评估使用HNE-1和CNE-2细胞的细胞摄取效率。发现载有双重药物，叶酸和PEG活化的ZnO纳米粒子的尺寸非常小，具有较高的Zeta电位和多分散指数，并且包封率也很高（82％）。纳米颗粒制剂具有稳定性并且当长时间保持分散形式时不会聚集。此外，发现它们与正常细胞孵育时具有可忽略的副作用，且具有细胞相容性。与游离形式相比，它们还表现出更高的细胞吸收效率。因此，可以安全地得出结论，组合药物负载，叶酸和