Abstract
Gold nanoparticles (AuNPs) and the pH stimuli-responsive drug delivery system have been extensively applied in cancer treatment. Carrageenan derived from marine red algae shows a promising application prospect for drug delivery as a nanomaterial for its biodegradability, abundance, and non-toxicity. Carrageenan oligosaccharide (CAO) was used as a biocompatible reductant for green synthesis of CAO-AuNPs, and the obtained CAO-AuNPs were further used as a delivery system for pH-triggered delivery of epirubicin (EPI). The EPI-CAO-AuNPs were demonstrated to be spherical and homogeneous with mean diameter of 141 ± 6 nm by means of electron microscopy and Malvern particle size analyzer. Results showed that the release of EPI from EPI-CAO-AuNPs was significant under acidic condition that simulated cancer environment, while it was negligible under physiological pH in vitro. Confocal laser scanning microscope and flow cytometry analysis showed that EPI-CAO-AuNPs were localized in cellular nucleus and induced more apoptosis of HCT-116 and HepG2 cells than free EPI. A new pH-triggered anticancer drug release was achieved by EPI-CAO-AuNPs system for the first time. The developed EPI-CAO-AuNPs nanosystem shows a promising prospect for pH-triggered delivery of antitumor drugs, and our work provides a new idea for targeted drug delivery by using biocompatible marine carbohydrates as nanomaterial.
Highlights
The targeted drug delivery system has attracted increasing attention in cancer treatment in the last decades
The Carrageenan oligosaccharide (CAO)-AuNPs system was adjusted to pH 9–10 and epirubicin hydrochloride (EPI.HCl) was added drop by drop into the system to produce a high-load non-ionized EPI nanosystem[15]
The negatively charged CAO-AuNPs could electrostatically interact with positively charged EPI under alkaline conditions, and the H-bonds were generated between protonated N atom of EPI and -OH of CAO-AuNPs16,17, which all were beneficial to form stable EPI-CAO-AuNPs system
Summary
The targeted drug delivery system has attracted increasing attention in cancer treatment in the last decades. AuNPs can accumulate in target cells through endocytosis and have been used as a targeted carrier for antitumor drug delivery[1,2,3]. We successfully prepared a stable and biocompatible AuNPs by usingcarrageenan oligosaccharide (CAO) derived from carrageenan to act as green reductant as well as stabilizer[7], and the obtained CAO-AuNPs exhibits a prospective application for drug delivery as a nanomaterial. Cancer cells apoptosis selected as a model drug and loaded in the CAO-AuNPs delivery nano-system to release drug with pH-responsive in vitro for the first time. The obtained EPI-CAO-AuNPs nanosystem was characterized and the cellular uptake and anti-cancer activity were investigated (Fig. 1)
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