Investigating folate-conjugated combinatorial drug loaded ZnO nanoparticles for improved efficacy on nasopharyngeal carcinoma cell lines

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.