Mesoporous polydopamine nanoparticles coated with metal-polyphenol networks for demethylation therapy of lung cancer

The treatment of lung cancer with azacitidine (AZA) is urgently in need of a novel delivery material due to its limitations, including a short half-life, high cytotoxicity, and poor tumor targeting. To overcome these limitations, the coordination of Gallic acid-catechin-gallate with Fe 3+ and its encapsulation on the surface of mPDA loaded with AZA (mA@EF) was prepared. mA@EF exhibited a uniform distribution of regular spherical particles with good stability and drug release properties. In cell experiments, mA@EF effectively inhibited cell viability, promoted cellular uptake, and downregulated the expression of DNA methyltransferases. Moreover, mA@EF demonstrated good biosafety. In animal experiments, mA@EF showed strong tumor-targeting and retention activity, and significantly inhibited the growth of tumor. This discovery provided a feasible dosing regimen for AZA treatment in lung cancer patients.