Multi-stimuli responsive Cu-MOFs@Keratin drug delivery system for chemodynamic therapy

Abstract

Although the potential of metal-organic framework (MOF) nanoparticles as drug delivery systems (DDS) for cancer treatment has been established by numerous studies, their clinical applications are still limited due to relatively poor biocompatibility. We fabricated a multifunctional Cu-MOFs@Keratin DDS for loaded drug and chemodynamic therapy (CDT) against tumor cells. The Cu-MOFs core was prepared using a hydrothermal method, and then loaded with the anticancer drug DOX and wrapped in human hair keratin. The Cu-MOFs@Keratin was well characterized by transmission electron microscopy (TEM), fourier transform infrared spectroscopy (FTIR), dynamic light scattering (DLS), and X-ray photoelectron spectroscopy (XPS). Characterization and pharmacokinetic studies of Cu-MOFs@Keratin were performed in vitro and in vivo. The keratin shell reduced the cytotoxicity and potential leakage of Cu-MOFs to normal cells, and allowed the drug-loaded nanoparticles to accumulate in the tumor tissues through enhanced permeability and retention effect (EPR). The particles entered the tumor cells via endocytosis and disintegrated under the stimulation of intracellular environment, thereby releasing DOX in a controlled manner. In addition, the Cu-MOFs produced hydroxyl radicals (·OH) by consuming presence of high intracellular levels of glutathione (GSH) and H2O2, which decreased the viability of the tumor cells.

Drug delivery system for the extended-release of larotrectinib based on a biocompatible Fe-based metal-organic framework: synthesis, characterization, in vitro release properties and antitumor evaluation

“…The FTIR spectrum of the Lar and Fe-MOF physical mixture was obtained by superimposing the spectra of the two individual components. While the positions of the characteristic absorption peaks of the drug and the material in the drug-loaded nanoparticles (Lar@Fe-MOF) remained the same, the kurtosis became slightly smaller, indicating that the drug was successfully wrapped with or adsorbed into the material ( Du et al, 2023 ; Karimi et al, 2023 ).…”

“…Frontiers in Bioengineering and Biotechnology frontiersin.org drug and the material in the drug-loaded nanoparticles (Lar@ Fe-MOF) remained the same, the kurtosis became slightly smaller, indicating that the drug was successfully wrapped with or adsorbed into the material (Du et al, 2023;Karimi et al, 2023).…”

Prospects, advances and biological applications of MOF-based platform for the treatment of lung cancer

“…Du et al synthesised Cu-MOFs@Keratin by hydrothermally preparing CuMOFs nuclei with the drug DOX and encapsulating them in human hair keratin (Keratin). 63 The nanoparticle synthesis and mechanism of action are shown in Fig. 7, which suggests that the nanoparticles produced Cu + by depleting GSH, and Cu + catalysed the production of toxic ˙OH from H 2 O 2 by the Fenton reaction at low pH, which led to apoptosis.…”

Metal-Organic Frameworks: Versatile Platforms for Biomedical Innovations

“…IRMOF-16 was studied as a potential pH-responsive drug delivery carrier for curcumin and exhibited pH-dependent behavior in the delivery process. Du et al [ 28 ] investigated the Cu-MOFs@Keratin drug delivery system, which demonstrated responsiveness to pH and ROS, with enhanced drug release observed under acidic and oxidative conditions.…”