The clinical translation of many inorganic nanomaterials is severely hampered by toxicity issues because of the long-term retention of these nanomaterials in the body. In this study, we developed a bio-clearable thera...The clinical translation of many inorganic nanomaterials is severely hampered by toxicity issues because of the long-term retention of these nanomaterials in the body. In this study, we developed a bio-clearable theranostic agent based on ultra-small MoS2 nanodots, which were synthesized by a facile bottom-up approach through one-step solvothermal decomposition of ammonium tetrathiomolybdate. After modification by glutathione (GSH), the obtained MoS2-GSH nanodots exhibited sub-10-nm hydrodynamic diameters without aggregation in various physiological buffers. Without showing appreciable in vitro toxicity, such MoS2-GSH nanodots with strong near-infrared (NIR) absorbance could induce remarkable photothermal ablation of cancer cells. Upon intravenous (i.v.) injection, efficient tumor accumulation of MoS2-GSH nanodots was observed by photoacoustic imaging, and further confirmed by analysis of the biodistribution of Mo. Notabl)4 the MoS2-GSH nanodots, in contrast to conventional MoS2 nanoflakes with larger sizes, showed rather efficient body clearance via urine, where the majority of the injected dose was cleared within just seven days. Photothermal ablation of tumors on mice was then realized with the MoS2-GSH nanodots, achieving excellent therapeutic efficacy. This study presents a new type of ultra-small nanoparticle with efficient tumor homing/treatment abilities, as well as rapid body clearance behavior, making it promising for cancer theranostics without long-term toxiciW concerns.展开更多
The integration of strong near-infrared(NIR)emission,rapid lysosome escape,fast cellular excretion,and efficient total body clearance is highly desired for nanoparticles(NPs)to achieve synergistic functions in both mo...The integration of strong near-infrared(NIR)emission,rapid lysosome escape,fast cellular excretion,and efficient total body clearance is highly desired for nanoparticles(NPs)to achieve synergistic functions in both molecular imaging and delivery.Herein,using a well-designed cyclopeptide(CP)that can spontaneously assem ble into controllable nanofibers a s template,a facile strategy is reported for in situ self-assembly of NIR-emitting gold NPs(AuNPs)into ordered and well-controlled one-dimensional(1D)nanostructures(AuNPs@CP)with greatly enhanced NIR emission(〜6 fold).Comparing with the unassem bled AuNPs,the AuNPs@CP are observed to enter living cells through endocytosis,escap e from lysosome rapidly,and excrete the cell fast,which shows high gene transfection efficiencies in construction of cell line with-7.5-fold overexpression of p53 protein.Furthermore,the AuNPs@CP exhibit high in vivo diffusibility and total body clearance efficiency with minimized healthy organ retention,which are also demonstrated to be good nanovectors for plasmid complementary deoxyribonucleic acid 3.1(pcDNA3.1)(+)-internal ribosome entry site(IRES)-green fluorescent protein(GFP)-p53 plasmid with efficient p53 gene over-expression in tumor site.This facile in situ strategy in fabricating highly luminescent 1D nanostructures provides a promising approach toward future translatable multifunctional nanostructures for delivering,tracking,and therapy.展开更多
基金This work was supported by the National Natural Science Foundation of China (Nos. 51525203, 51302180, and 51572180), the National Basic Research Program of China (No. 2012CB932601). We acknowledge Collaborative Innovation Center of Suzhou Nano Science & Technology., the Priority Academic Program Development (PAPD) of Jiangsu Higher Education Institutions. T. L. was supported by a scholarship from the China scholarship Council (CSC).
文摘The clinical translation of many inorganic nanomaterials is severely hampered by toxicity issues because of the long-term retention of these nanomaterials in the body. In this study, we developed a bio-clearable theranostic agent based on ultra-small MoS2 nanodots, which were synthesized by a facile bottom-up approach through one-step solvothermal decomposition of ammonium tetrathiomolybdate. After modification by glutathione (GSH), the obtained MoS2-GSH nanodots exhibited sub-10-nm hydrodynamic diameters without aggregation in various physiological buffers. Without showing appreciable in vitro toxicity, such MoS2-GSH nanodots with strong near-infrared (NIR) absorbance could induce remarkable photothermal ablation of cancer cells. Upon intravenous (i.v.) injection, efficient tumor accumulation of MoS2-GSH nanodots was observed by photoacoustic imaging, and further confirmed by analysis of the biodistribution of Mo. Notabl)4 the MoS2-GSH nanodots, in contrast to conventional MoS2 nanoflakes with larger sizes, showed rather efficient body clearance via urine, where the majority of the injected dose was cleared within just seven days. Photothermal ablation of tumors on mice was then realized with the MoS2-GSH nanodots, achieving excellent therapeutic efficacy. This study presents a new type of ultra-small nanoparticle with efficient tumor homing/treatment abilities, as well as rapid body clearance behavior, making it promising for cancer theranostics without long-term toxiciW concerns.
基金the National Natural Science Foundation of China(Nos.21573078,22022403)Guangdong Natural Science Funds for Distinguished Young Scholars(No.2016A030306024)+1 种基金Guangzhou Science and Technology Project(No.201904010055)Fundamental Research Funds for the Central Universities.
文摘The integration of strong near-infrared(NIR)emission,rapid lysosome escape,fast cellular excretion,and efficient total body clearance is highly desired for nanoparticles(NPs)to achieve synergistic functions in both molecular imaging and delivery.Herein,using a well-designed cyclopeptide(CP)that can spontaneously assem ble into controllable nanofibers a s template,a facile strategy is reported for in situ self-assembly of NIR-emitting gold NPs(AuNPs)into ordered and well-controlled one-dimensional(1D)nanostructures(AuNPs@CP)with greatly enhanced NIR emission(〜6 fold).Comparing with the unassem bled AuNPs,the AuNPs@CP are observed to enter living cells through endocytosis,escap e from lysosome rapidly,and excrete the cell fast,which shows high gene transfection efficiencies in construction of cell line with-7.5-fold overexpression of p53 protein.Furthermore,the AuNPs@CP exhibit high in vivo diffusibility and total body clearance efficiency with minimized healthy organ retention,which are also demonstrated to be good nanovectors for plasmid complementary deoxyribonucleic acid 3.1(pcDNA3.1)(+)-internal ribosome entry site(IRES)-green fluorescent protein(GFP)-p53 plasmid with efficient p53 gene over-expression in tumor site.This facile in situ strategy in fabricating highly luminescent 1D nanostructures provides a promising approach toward future translatable multifunctional nanostructures for delivering,tracking,and therapy.