High‐Efficient Clearable Nanoparticles for Multi‐Modal Imaging and Image‐Guided Cancer Therapy

Renal‐clearable nanoparticles have made it possible to overcome the toxicity by nonspecific accumulation in healthy tissues/organs due to their highly efficient clearance characteristics. However, their tumor uptake is relatively low due to the short blood circulation time and rapid body elimination. Here, this problem is addressed by developing renal‐clearable nanoparticles by controlled coating of sub‐6 nm CuS nanodots (CuSNDs) on doxorubicin ladened mesoporous silica nanoparticles (pore size ≈6 nm) for multimodal application. High tumor uptake of the as‐synthesized nanoparticles (abbreviated as MDNs) is achieved due to the longer blood circulation time. The MDNs also show excellent performance in bimodal imaging. Moreover, the MDNs demonstrated a photothermally sensitive drug release and pronounced synergetic effects of chemo‐photothermal therapy, which were confirmed by two different tumor models in vivo. A novel key feature of the proposed synthesis is the use of renal‐clearable CuSNDs and biodegradable mesoporous silica nanoparticles which also are renal‐clearable after degradation. Therefore, the MDNs would be rapidly degraded and excreted in a reasonable period in living body and avoid long‐term toxicity. Such biodegradable and clearable single‐compartment theranostic agents applicable in highly integrated multimodal imaging and multiple therapeutic functions may have substantial potentials in clinical practice. Highly efficient clearable theranostic ultrasmall CuS nanodots@mesoporous silica nanoparticles with high tumor uptake are synthesized, and demonstrated to be capable for positron emission tomography/photoacoustic bimodal imaging, imaging‐guided effective combined chemo‐photothermal therapy, and high‐efficient body clearance.