Functionalized halloysite nanotube by chitosan grafting for drug delivery of curcumin to achieve enhanced anticancer efficacy

Abstract

Halloysite nanotubes (HNTs) have a unique tubular structure in nanoscale, and have shown potential as novel carriers for various drugs. Coating the nanotubes with a hydrophilic polymer shell can significantly decrease the toxicity and provide colloidal stability during blood circulation. Here, we synthesized chitosan grafted HNTs (HNTs-g-CS) and investigated their potential as a nano-formulation for the anticancer drug curcumin. The structure and properties of HNTs-g-CS were characterized using water contact angle, zeta-potential, Fourier transform infrared (FTIR) spectroscopy, thermogravimetric analysis (TGA), and transmission electron microscopy (TEM) techniques. HNTs-g-CS exhibit a maximum 90.8% entrapment efficiency and 3.4% loading capacity of curcumin, which are higher than those of raw HNTs. HNTs-g-CS also show no obvious hemolytic phenomenon and good stability in serum. The cumulative release ratio of curcumin from HNTs-g-CS/curcumin at cell lysate after 48 hours is 84.2%. The curcumin loaded HNTs-g-CS show specific toxicity to various cancer cell lines, including HepG2, MCF-7, SV-HUC-1, EJ, Caski and HeLa, and demonstrate an inhibition concentration of IC₅₀ at 5.3–192 μM as assessed by cytotoxicity studies. The anticancer activity of this nanoformulation is extremely high in EJ cells compared with the other cancer cell lines. The cell uptake of HNTs-g-CS is confirmed by fluorescence microscopy. Flow cytometric analysis of curcumin loaded HNTs-g-CS shows that curcumin loaded HNTs-g-CS increase apoptosis on EJ cells. The content of ROS created by HNTs-g-CS/curcumin is more than that of free curcumin. All these results suggest that HNTs-g-CS are potential nanovehicles for anticancer drug delivery in cancer therapy.