Optimizing the Size of Zr-Based Metal–Organic Frameworks for Enhanced Anticancer Efficacy

Metal-organic frameworks (MOFs) have great potential for drug delivery systems due to their tunnel pore size, structural versatility, and high surface area. Among them, UiO-67 have recently attracted substantial attention as functional nanocarriers for effective delivery of small molecule chemical drugs. However, the influence of the size on cellular uptake of UiO-67 remains ambiguous. Here, we use polyvinyl pyrrolidone (PVP) as the capping agent of UiO-67 to synthesize spherical Zr-based MOFs with various diameters, including 40 nm, 60 nm, and 120 nm. The highest cellular uptake is observed in the case of Zr-based MOFs with a diameter of 40 nm (PU₄₀ MOFs). Moreover, doxorubicin can be loaded into the inner pores of PU₄₀ MOF via π-π and electrostatic interactions (DPU₄₀ MOFs), with a loading capacity of 82 wt%, and gradually released under acidic conditions. In vitro, the resulting DPU₄₀ MOFs can be internalized by cancer cells more effectively, thereby enhancing the delivery of doxorubicin into cancer cells. Ultimately, this results in enhanced antitumor efficacy toward 4T1, Hs 578T, and MCF-7 cells. Our findings indicate that approximately 40 nm may be the optimum diameter for the special Zr-based MOFs to be internalized by cells more effectively, providing potent potential nanocarriers for drug delivery.