Gold nanocomposites in colorectal cancer therapy: characterization, selective cytotoxicity, and migration inhibition

The third most prevalent type of cancer in the world, colorectal cancer, poses a significant treatment challenge due to the nonspecific distribution, low efficacy, and high systemic toxicity associated with chemotherapy. To overcome these limitations, a targeted drug delivery system with a high cytotoxicity against cancer cells while maintaining a minimal systemic side effects represents a promising therapeutic approach. Therefore, the aim of this study was to develop an efficient gold nanocarrier for the targeted delivery of the anticancer agent everolimus to Caco-2 cells. A novel gold nanocomposite (EV-β-CD-HA-Chi-AuNCs) functionalized with a targeting ligand (hyaluronic acid), a permeation enhancement excipient (chitosan), and an anticancer inclusive compound consisting of beta-cyclodextrin and everolimus was proposed and prepared via Turkevich method. Characterization was performed with a UV spectrometer, FTIR, Zetasizer, and HRTEM. Its drug release profile was also evaluated in media with three different pH values. Cytotoxicity and biocompatibility studies were performed on a colorectal cancer cell line (Caco-2) and a normal fibroblast line (MRC-5), respectively, via xCELLigence real-time cellular analysis (RTCA) technology. The inhibitory effect on migration was also further tested via the xCELLigence RTCA technique and a scratch assay. Characterization studies revealed the successful formation of EV-β-CD-HA-Chi-AuNCs with a size and charge which are suitable for the use as targeted drug delivery carrier. In the cytotoxic study, the EV-β-CD-HA-Chi-AuNCs showed a lower IC₅₀ (16 ± 1 µg/ml) than the pure drug (25 ± 3 µg/ml) toward a colorectal cell line (Caco-2). In the biocompatibility study, the EV-β-CD-HA-Chi-AuNCs have minimal toxicity, while the pure drug has severe toxicity toward healthy fibroblasts (MRC-5) despite its low concentration. In the cell migration study, the EV-β-CD-HA-Chi-AuNCs also showed a greater inhibitory effect than the pure drug. Compared with the pure drug, the EV-β-CD-HA-Chi-AuNCs exhibit an excellent selective cytotoxicity between cancerous colorectal Caco-2 cells and healthy MRC-5 cells, making it a potential carrier to carry the drug to the cancerous site while maintaining its low toxicity to the surrounding environment. In addition, an increase in the cytotoxic activity of the EV-β-CD-HA-Chi-AuNCs toward cancerous colorectal Caco-2 cells was also observed, which can potentially improve the treatment of colorectal cancer.