A facile synthesis of uniform hollow MIL-125 titanium-based nanoplatform for endosomal esacpe and intracellular drug delivery.

• A facile approach to synthesize biocompatible hollow-structured MIL-125-Ti nano-MOFs. • The optimal MIL-125-Ti-HA nanoparticles were synthesized for delivery of doxorubicin. • The NPs had high DOX loading contents with pH-sensitive release. • The NPs could escape from lysosomes to improve intracellular drug accumulation. Metal-organic-frameworks (MOFs) have been widely used for drug delivery systems due to their high drug loading content and easy modification. But it remains the biggest challenge to exploring biocompatible MOFs with uniform small sizes and well-defined surface chemistry for tumor therapy. Especially, the hollow-structured MIL-125 Titanium (Ti) nano-MOFs have not been prepared for drug carriers. Therefore, we studied a facile approach to synthesize hollow-structured Ti-based nano-MOF via surfactant coordination modulation. The as-prepared nanomaterials exhibited uniform size of ~200 nm and large BET surface area of 1134 m2·g−1. And then, by simple mechanical grinding, we prepared this hyaluronic acid (HA) modified Ti-based MOFs. Moreover, the amount of HA modification on the MOFs surface for the drug delivery systems was systematically investigated. The doxorubicin (DOX) loaded nano-MOFs (MIL-125-Ti@DOX) and HA modified nanomaterials (MIL-125-Ti-HA@DOX) possessed high doxorubicin loading content (~25.0–35.0%) due to their hollow structures and π-π stacking interaction. Especially, In vitro and in vivo safety assessments proved that the Ti-based nano MOF was non-toxic and biocompatibility. Besides, MIL-125-Ti-HA@DOX could escape from lysosomes to improve intracellular drug accumulations resulting in the enhanced the anticancer efficacy. In vivo antitumor results demonstrated that MIL-125-Ti-HA@DOX could not only enhance targeted tumor therapy but also lower the side effect of DOX. Therefore, the novel hollow MIL-125-Ti-HA@DOX as a promising nanoplatform could be applied to targeted tumor therapy. [ABSTRACT FROM AUTHOR]