Novel amphiphilic rhamnogalacturonnan I-based nanomicelles for targeted delivery of curcumin to hepatocellular carcinoma cells

Curcumin (Cur) is a bioactive nutraceutical with great potential in biological, nutritional, and medical applications. However, these applications are limited by various factors such as insufficient ingestion, low aqueous solubility, and relatively high toxicity to normal cells. To tackle these obstacles, we synthesized a novel Cur-modified-rhamnogalacturonan (RG-C) nano-micelle carrier to target-deliver Cur to hepatocellular carcinoma HepG2 cells via specific recognition of RG-I by the overexpressed surface galactin-3 receptor. Fourier transfer infrared, UV-vis, and H-1 NMR analyses confirmed the conjugation between RG and Cur RG-C loaded with Cur (RG-CC) was formed via self-assembly in an aqueous solution with a drug loading efficiency of 12.2%. RG-CC micelle was ellipsoidal or cubic with a size ranging between 100 and 200 nm by scanning electron microscopy observation. Cur release from RG-CC exhibited a controlled and pH-dependent manner with 50% at pH 5.0 in contrast to 5% at pH 7.4 after 24 h exposure. RG-CC possessed more potent anti-proliferative activity against HepG2 cells than normal embryonic kidney 293T cells. Compared to free Cur, both the anti-proliferative effect and uptake of RG-CC were significantly higher in HepG2 cells as revealed from laser confocal microscopy and flow cytometry analyses. RG-CC was a promising anticancer candidate and deserves further preclinical and clinical investigations.