Promotion of the anticancer activity of curcumin based on a metal-polyphenol networks delivery system.

Abstract Curcumin (Cur), a hydrophobic active pharmaceutical ingredient with high anticancer activity, has poor water solubility and low bioavailability. Although many delivery systems have been developed to improve their bioavailability, some limitation such as low drug loading efficiency and poor stability are still remained. The metal-polyphenol networks (MPNs) delivery system designed in this subject solved above problems and effectively improved the anticancer activity of Cur. The synthesized Cur@EGCG-Fe(III) is consisting of epigallocatechin gallate (EGCG), iron chloride (FeCl3) and Cur, and the well-designed structure endow Cur@EGCG-Fe(III) high loading efficiency, good water solubility and stability. After the Cur@EGCG-Fe(III) nanoparticles were internalized by MCF-7 cells, the Cur could be released in endo/lysosomal microenvironment (pH=5.0), and the Cur delivery in the deep tumor could be realized. The distribution of Cur@EGCG-Fe(III) in MCF-7 cells was analyzed by laser confocal, and Cur@EGCG-Fe(III) could effectively deliver more Cur into MCF-7 cells in comparison with free Cur. In addition, the results of flow cytometry and western blot further indicated that Cur@EGCG-Fe(III) had a stronger ability to induce apoptosis than free Cur. Transwell cell migration and invasion experiments showed that Cur and EGCG-Fe(III) had a synergistic effect in inhibiting MCF-7 cell migration and invasion. In vitro hemolysis and in vivo experiments showed that the Cur@EGCG-Fe(III) had negligible effect on the blood environment and a great tumor-inhibition efficacy, indicating that the MPNs delivery system had a good blood compatibility and antitumor activity. Our results indicated that MPNs-coated Cur nanoparticle could be a new form of Cur delivery system for anticancer application.