Due to the ability to combine the separately unique characteristics of assembled and disassembled nanoparticles(NPs), the stimuli-responsive self-assembly of NPs has attracted considerable interest in functional mater...Due to the ability to combine the separately unique characteristics of assembled and disassembled nanoparticles(NPs), the stimuli-responsive self-assembly of NPs has attracted considerable interest in functional material applications especially biomaterials. Here we demonstrate a facile and versatile approach to regulate the self-assembly process and transition pH of Au NPs by fine-tuning the co-modified pH-responsive compounds and poly(ethylene glycol)(PEG). Importantly the transition pH(ΔpH=0.4) of the system can be predetermined in the range of 8.2–5.8(assembled to disassembled) and 8.2–4.2(disassembled to assembled), which ideally covers the pH of normal tissue, tumor tissue milieu and organelles. The results of fluorescence imaging, Raman spectroscopy and photothermal conversion of the stimuli-responsive Au NPs shows the potential application for tumor specificity theranostics. In a nutshell this study provides a useful toolkit to design tumor-activatable self-assembled NPs with high specificity and universality.展开更多
Atherosclerotic cardiovascular disease is the leading cause of mortality in the world.A driving feature of atherosclerotic plaque formation is dysfunctional efferocytosis.Because the“don’t eat me”molecule CD47 is u...Atherosclerotic cardiovascular disease is the leading cause of mortality in the world.A driving feature of atherosclerotic plaque formation is dysfunctional efferocytosis.Because the“don’t eat me”molecule CD47 is upregulated in atherosclerotic plaque cores,CD47-blocking strategies can stimulate the efferocytic clearance of apoptotic cells and thereby help prevent the progression of plaque buildup.However,these therapies are generally costly and,in clinical and murine trials,they have resulted in side effects including anemia and reticulocytosis.Here,we developed and characterized an intracellular phagocytosis-stimulating treatment in the CD47-SIRPαpathway.We loaded a novel monocyte/macrophage-selective nanoparticle carrier system with a small molecule enzymatic inhibitor that is released in a pH-dependent manner to stimulate macrophage efferocytosis of apoptotic cell debris via the CD47-SIRPαsignaling pathway.We demonstrated that single-walled carbon nanotubes(SWNTs)can selectively deliver tyrosine phosphatase inhibitor 1(TPI)intracellularly to macrophages,which potently stimulates efferocytosis,and chemically characterized the nanocarrier.Thus,SWNT-delivered TPI can stimulate macrophage efferocytosis,with the potential to reduce or prevent atherosclerotic disease.展开更多
A major impediment in the development of chitosan nanoparticles （CTS NPs） as effective drug delivery vesicles is their rapid clearance from blood and endosome entrapment. To overcome these problems, a convenient and...A major impediment in the development of chitosan nanoparticles （CTS NPs） as effective drug delivery vesicles is their rapid clearance from blood and endosome entrapment. To overcome these problems, a convenient and promising template system was developed by decorating poly（methacrylic acid） （PMAA） to the surface of 10-hydroxy camptothecin （HCPT）-loaded CTS NPs （HCPT-CTS/ PMAA NPs）. The results show that the presence of negatively charged PMAA significantly elongated the blood circulation time of HCPT-CTS NPs from 12 to 24 h, and reduced the blood clearance （C1） from 30.57 to 6.72 mL/h in vivo. The calculated area under curve （AUC0-24h） and terminal elimination half-life （tl/2） of HCPT-CTS/PMAA NPs were 4.37-fold and 2.48-fold compared with those of HCPT-CTS NPs. Furthermore, the positively charged HCPT-CTS/PMAA NPs triggered by tumor acidic microenvironment （pH 6.5） result in a 453-fold higher cellular uptake than the negatively charged counterparts at pH 7.4. Additionally, HCPT-CTS/PMAA NPs have the ability to escape endosomal entrapment via ＂proton sponge effect＂ after incubation with HepG2 cells for 3 h at pH 6.5. Taken together, these findings open up a convenient, low-cost, but effective way to prepare HCPT-CTS/PMAA NPs as a candidate for developing vectors with enhanced long blood circulation and endosomal escape ability in future clinical experiments.展开更多
基金supported by the National Natural Science Foundation of China(51433004,51773096)the Natural Science Foundation of Tianjin(17JCZDJC33500)and PCSIRT(IRT1257)
文摘Due to the ability to combine the separately unique characteristics of assembled and disassembled nanoparticles(NPs), the stimuli-responsive self-assembly of NPs has attracted considerable interest in functional material applications especially biomaterials. Here we demonstrate a facile and versatile approach to regulate the self-assembly process and transition pH of Au NPs by fine-tuning the co-modified pH-responsive compounds and poly(ethylene glycol)(PEG). Importantly the transition pH(ΔpH=0.4) of the system can be predetermined in the range of 8.2–5.8(assembled to disassembled) and 8.2–4.2(disassembled to assembled), which ideally covers the pH of normal tissue, tumor tissue milieu and organelles. The results of fluorescence imaging, Raman spectroscopy and photothermal conversion of the stimuli-responsive Au NPs shows the potential application for tumor specificity theranostics. In a nutshell this study provides a useful toolkit to design tumor-activatable self-assembled NPs with high specificity and universality.
基金This study was funded by an AHA Transformational Project grant(No.18TPA34230113),NIH R01 CA244491,and Falk Catalyst grant.
文摘Atherosclerotic cardiovascular disease is the leading cause of mortality in the world.A driving feature of atherosclerotic plaque formation is dysfunctional efferocytosis.Because the“don’t eat me”molecule CD47 is upregulated in atherosclerotic plaque cores,CD47-blocking strategies can stimulate the efferocytic clearance of apoptotic cells and thereby help prevent the progression of plaque buildup.However,these therapies are generally costly and,in clinical and murine trials,they have resulted in side effects including anemia and reticulocytosis.Here,we developed and characterized an intracellular phagocytosis-stimulating treatment in the CD47-SIRPαpathway.We loaded a novel monocyte/macrophage-selective nanoparticle carrier system with a small molecule enzymatic inhibitor that is released in a pH-dependent manner to stimulate macrophage efferocytosis of apoptotic cell debris via the CD47-SIRPαsignaling pathway.We demonstrated that single-walled carbon nanotubes(SWNTs)can selectively deliver tyrosine phosphatase inhibitor 1(TPI)intracellularly to macrophages,which potently stimulates efferocytosis,and chemically characterized the nanocarrier.Thus,SWNT-delivered TPI can stimulate macrophage efferocytosis,with the potential to reduce or prevent atherosclerotic disease.
文摘A major impediment in the development of chitosan nanoparticles （CTS NPs） as effective drug delivery vesicles is their rapid clearance from blood and endosome entrapment. To overcome these problems, a convenient and promising template system was developed by decorating poly（methacrylic acid） （PMAA） to the surface of 10-hydroxy camptothecin （HCPT）-loaded CTS NPs （HCPT-CTS/ PMAA NPs）. The results show that the presence of negatively charged PMAA significantly elongated the blood circulation time of HCPT-CTS NPs from 12 to 24 h, and reduced the blood clearance （C1） from 30.57 to 6.72 mL/h in vivo. The calculated area under curve （AUC0-24h） and terminal elimination half-life （tl/2） of HCPT-CTS/PMAA NPs were 4.37-fold and 2.48-fold compared with those of HCPT-CTS NPs. Furthermore, the positively charged HCPT-CTS/PMAA NPs triggered by tumor acidic microenvironment （pH 6.5） result in a 453-fold higher cellular uptake than the negatively charged counterparts at pH 7.4. Additionally, HCPT-CTS/PMAA NPs have the ability to escape endosomal entrapment via ＂proton sponge effect＂ after incubation with HepG2 cells for 3 h at pH 6.5. Taken together, these findings open up a convenient, low-cost, but effective way to prepare HCPT-CTS/PMAA NPs as a candidate for developing vectors with enhanced long blood circulation and endosomal escape ability in future clinical experiments.
