PVP-modulated preparation of size-tunable Cu-MOF exhibiting good bactericidal effect and drug-release controlled behavior to efficiently kill tumor cell

Metal-organic frameworks (MOFs), such as Cu-MOF, have emerged as highly efficient tumor drug carriers due to their tunable particle size, adequate adsorption property, and good biocompatibility. In this work, Cu-MOFs with different sizes were synthesized by employing a micelle-confined strategy via controlling the concentration of the polyvinylpyrrolidone (PVP) template. At a PVP concentration of 400 mM, the X-ray diffraction (XRD), scanning electron microscopy (SEM), and X-ray photoelectron spectroscopy (XPS) results jointly confirmed that Cu-MOF nanoparticles (named as Cu-MOF- 400 ) with an average grain size of 167 nm were successfully synthesized. The Cu-MOF -400 exhibited a good crystal structure with the regular octahedral morphology, and possessed a pore diameter of about 1.83 nm with the elements (Cu, C, and O) distributed evenly on the surfaces. In vitro co-culturing experiments revealed that the Cu-MOF -400 exhibited low cytotoxicity to 293T cells, while achieving antibacterial inhibition rates of 58.3% and 69.1% against Gram-negative bacteria ( Escherichia coli ) and Gram-positive bacteria ( Staphylococcus aureus ), respectively. With the aid of the pore structure, Cu-MOF- 400 had a drug loading efficiency (DLE) of 78.3% for doxorubicin (DOX) within 24 h, and the DOX-loaded system (named as Cu-MOF -400 @DOX) demonstrated significant pH-responsive drug release properties in the tumor microenvironment (pH 5.2), with a cumulative release rate of 54.75% over 72 h, which is 6.3 times higher compared to that under the physiological conditions (pH 7.4), fitting well to the Korsmeyer-Peppas model. In addition, Cu-MOF -400 @DOX inhibited the survival of HeLa tumor cells to 42.2% (a killing rate of 57.8%) at a concentration of 9 μg·mL -1 , which might be due to the good cellular-uptake effect of the drug-loaded system; as the Cu-MOF -400 @DOX achieved complete intracellular localization within 6 h, which significantly facilitated the acid-triggered DOX release. With good cytocompatibility and bactericidal effect, and after DOX loading, the nanosystem displays excellent pH-responsive drug release to efficiently suppress tumor-cell growth in vitro, offering a new strategy for the development of new-type drugs in clinic for tumor treatment and bacterial resistance prevention.