Simultaneous Multimodal Imaging And Photothermal Therapy Via Renal-clearable Manganese-doped Copper Sulfide Nanodots

Nanoparticles are to be promising tools for preclinical research for cancer detection and treatment owing to their unique physical and chemical properties.However,plenty of investigations show that the long-time retention problem resulting from the non-specific accumulation of nanoparticles in the mononuclear phagocyte system(MPS),and the relatively slow liver clearance into bile,cause many inevitable side effects.Furthermore,compared to the liver clearance pathway,the renal-urinary route is considered more desirable for its rapidity,which could reduce the toxicity of nanoparticles accumulated in vivo and lead to a quick reduction of background signals during diagnostic imaging and thus improves imaging quality.Therefore,the design of nanoparticles that have optimized surface charge and smaller size than the renal excretion threshold(<6 nm)can be cleared rapidly by kidneys and improves the safety for biomedical applications.In addition,compared with single modality counterparts,multimodality imaging are more desirable.multimodality imaging can combine satisfactory properties across the spatial resolution,sensitivity,and tissue penetration,which are often performed in different single-modality imaging.As a result,multimodality imaging can provide accurate physiological information to improve the accuracy of disease in clinic.In this study,we fabricated a triple imaging modalities and photothermal therapy(PTT)nanoparticle based on multifunctional ultrasmall CuS nanodots.We doped paramagnetic manganese2+(Mn2+)ions and a PET radioisotope gallium-68(68Ga)into the CuS matrix by chelator-free doping,using bovine serum albumin(BSA)as the synthesis template.More detailed information,such as tissue distribution,tumor accumulation,renal clearance,etc.,were achieved by the ultrasmall Mn-CuS@BSA NDs based triple-modal imaging,including magnetic resonance imaging(MRI),photoacoustic imaging(PAI)and positron emission tomography(PET).In this thesis,the multimodality imaging indicated the NDs had satisfactory efficiency in contrast enhancement of three modalities,providing sufficient information in tissue penetration,spatial resolution,and accuracy.Therefore,Mn/68Ga-CuS@BSA NDs can be applied for visualization,providing guidance for further cancer treatment.Meanwhile,PET imaging results showed that the signal of kidney and bladder was significantly enhanced after intravenous injection in SKOV3 ovarian tumor model,demonstrating that Mn/68Ga-CuS@BSA NDs can be efficiently cleared through the renal-urinary route.Moreover,the SKOV-3 cancer cells were significantly suppressed both in vitro and in vivo after irradiation of 980 nm near-infrared laser,resulting from the excellent photothermal killing effects.Based on our results,the renal-clearable NDs could induce enhanced multimodality imaging and efficient PTT,which has great potential preclinical and clinical implications for cancer diagnosis and treatment.