Highly Stable and Long‐Circulating Metal‐Organic Frameworks Nanoprobes for Sensitive Tumor Detection In Vivo

: High stability and extended circulation time in vivo are quite favorable for practical biomedical applications of nanomaterials, because they greatly facilitate the preferential tumor accumulation of nanomaterials, resulting in enhanced signal fidelity for imaging and improved therapeutic effect for treatment. Although many surface modification approaches have been employed to improve the stability and circulating behavior of nanomaterials, it still remains challenging in acquiring stable and long-lasting nanomaterials for in vivo bioimaging and therapy, especially for nanoscale metal-organic frameworks (NMOFs) due to their intrinsic instability in physiological conditions. Herein, a facile, one-step strategy is reported to encapsulate the zirconium (Zr)-based NMOF UiO-66 within 1,2-dioleoyl-sn-glycero-3-phosphate (DOPA) lipid bilayer (DOPA-LB). Contrary to UiO-66 NMOFs functionalized with polyethylene glycol, the obtained UiO-66@DOPA-LB presents significantly enhanced stability and impressive blood circulation time, allowing a higher accumulation of UiO-66@DOPA-LB in the tumor tissue. Benefited from these meritorious features, UiO-66@DOPA-LB labeled with near-infrared dye, IRDye 800CW, can not only achieve highly sensitive imaging of breast cancer tumor (5 mm), but also exhibits superior capability for early tumor (1-2 mm) detection. This study enriches the surface modification approach of NMOFs, and is of great importance for practical application of NMOFs in biomedical areas.