通过超声法制备了载多柔比星的透明质酸-聚组氨酸聚合物(HPH)胶束。结果所得胶束呈类球形,粒径为(212.2±11.9)nm,多分散系数为0.28±0.02,?电位为(-11.91±0.66)m V,包封率为(92.09±0.88)%,载药量为(7.24±0.46)...通过超声法制备了载多柔比星的透明质酸-聚组氨酸聚合物(HPH)胶束。结果所得胶束呈类球形,粒径为(212.2±11.9)nm,多分散系数为0.28±0.02,?电位为(-11.91±0.66)m V,包封率为(92.09±0.88)%,载药量为(7.24±0.46)%。体外释放结果显示载药胶束具有明显的p H依赖性。胶束在酸性(p H 5.0和6.0)介质中的释药速度明显高于在中性(p H 7.4)介质中。体外细胞毒性试验表明,空白载体对表面过表达CD44受体的肿瘤细胞MCF-7和A549以及正常细胞L929均无明显毒性;但载药胶束对肿瘤细胞的存活率具有明显抑制作用,且呈浓度依赖性,而即使胶束中1浓度达到10?g/ml,L929细胞的存活率仍接近60%。细胞摄取试验表明,载药胶束在肿瘤细胞中的相对摄取量显著大于正常细胞。展开更多
Although it is reported that the targeting ability of hyaluronic acid(HA)-based nanoparticles(NPs) is molecular weight(MW) dependent,the influence of HA MW on targeting efficiency of HA-functionalized NPs and the unde...Although it is reported that the targeting ability of hyaluronic acid(HA)-based nanoparticles(NPs) is molecular weight(MW) dependent,the influence of HA MW on targeting efficiency of HA-functionalized NPs and the underlying mechanism remain elusive. In this study,we constituted three HA-functionalized Dox-loaded NPs(Dox/HCVs) different HA MWs(7,63,and 102 k Da) and attempted to illustrate the effects of HA MW on the targeting efficiency.The three Dox/HCVs had similar physiochemical and pharmaceutical characteristics,but showed different affinity to CD44 receptor. Furthermore,Dox/HCV-63 exerted the best targeting effect and the highest cytotoxicity compared with Dox/HCV-7 and Dox/HCV-102. It was interesting to found that both the HA-CD44 binding affinity and induced CD44 clustering by HA-based NPs were HA MW-dependent,the two of which determine the apparent targeting efficacy of Dox/HCV NPs in the conflicting directions. Those results laid a good foundation for rationally designing HA-based NPs in cancer therapy.展开更多
This work aimed to develop an intelligent multi-target tracking hyaluronic acid-RGDchlorambucil-quantum dots（HA-RGD-CLB-QDs） drug delivery system. After deacetylated, hyaluronic acid was reacted with anticancer drug...This work aimed to develop an intelligent multi-target tracking hyaluronic acid-RGDchlorambucil-quantum dots（HA-RGD-CLB-QDs） drug delivery system. After deacetylated, hyaluronic acid was reacted with anticancer drug chlorambucil, RGD, and quantum dots to obtain the HA-RGD-CLB-QDs drug delivery system. The characterization by FT-IR, ~1 H NMR, TEM, XPS, DLS, and UV-vis absorption and fluorescence spectra show that the system is successfully constructed with an average particle size of about 70 nm. The results of the drug release profile show that that the system has a p H and enzyme sensitive controlled release behaviour. Moreover, cellular uptake and toxicity results show that the system has an ideal dual receptormediated endocytosis pathway that significantly enhances the efficacy of CLB tumor therapy and has a lower toxicity to normal cells.The system shows the potential application as a carrier for cancer therapy.展开更多
Kupffer cells, expressing toll-like receptor 4 (TLR4), play a central role in hepatic ischemia/reperfusion (I/R) injury. Hyaluronic acid (HA) fragments, degradative products of high-molecular-weight HA (HMW-HA), acqui...Kupffer cells, expressing toll-like receptor 4 (TLR4), play a central role in hepatic ischemia/reperfusion (I/R) injury. Hyaluronic acid (HA) fragments, degradative products of high-molecular-weight HA (HMW-HA), acquire the ability to activate immune cells under inflammatory conditions. Here we inves- tigated whether HA fragments could activate Kupffer cells and analyzed the underlying mechanism. Kupffer cells were isolated from wild-type mice (WT, C3H/HeN) and TLR4 mutant mice (C3H/HeJ) and HA fragments were produced by the methods of enzyme digestion and chromatography. Then Kupffer cells were stimulated by HA fragments or other control stimuli. The activation of Kupffer cells was estimated as the release of pro-inflammatory cytokines. The activation of p38 MAPK pathway of Kupffer cells was checked and blocking experiments were done as well. The results indicated that HA fragments acquired the ability to activate Kupffer cells in vitro, which was TLR4 dependent and not due to contamination of lipopolysaccharide. Experiments of p38 MAPK kinase inhibition by SB-203580 verified p38 MAPK was required in HA fragments induced Kupffer cells activation. This suggests that HA fragments, degradative products of one of the major glycosaminoglycans of the extracellular matrix, play critical roles in Kupffer cell activation mediated by TLR4 signaling pathway, which is, at least partially, de- pendent on p38 MAPK activation.展开更多
文摘通过超声法制备了载多柔比星的透明质酸-聚组氨酸聚合物(HPH)胶束。结果所得胶束呈类球形,粒径为(212.2±11.9)nm,多分散系数为0.28±0.02,?电位为(-11.91±0.66)m V,包封率为(92.09±0.88)%,载药量为(7.24±0.46)%。体外释放结果显示载药胶束具有明显的p H依赖性。胶束在酸性(p H 5.0和6.0)介质中的释药速度明显高于在中性(p H 7.4)介质中。体外细胞毒性试验表明,空白载体对表面过表达CD44受体的肿瘤细胞MCF-7和A549以及正常细胞L929均无明显毒性;但载药胶束对肿瘤细胞的存活率具有明显抑制作用,且呈浓度依赖性,而即使胶束中1浓度达到10?g/ml,L929细胞的存活率仍接近60%。细胞摄取试验表明,载药胶束在肿瘤细胞中的相对摄取量显著大于正常细胞。
基金supported by the National Basic Research Program of China (No. 81573371)the key projects of Liaoning Province Department of Education (No. 2017LZD03)
文摘Although it is reported that the targeting ability of hyaluronic acid(HA)-based nanoparticles(NPs) is molecular weight(MW) dependent,the influence of HA MW on targeting efficiency of HA-functionalized NPs and the underlying mechanism remain elusive. In this study,we constituted three HA-functionalized Dox-loaded NPs(Dox/HCVs) different HA MWs(7,63,and 102 k Da) and attempted to illustrate the effects of HA MW on the targeting efficiency.The three Dox/HCVs had similar physiochemical and pharmaceutical characteristics,but showed different affinity to CD44 receptor. Furthermore,Dox/HCV-63 exerted the best targeting effect and the highest cytotoxicity compared with Dox/HCV-7 and Dox/HCV-102. It was interesting to found that both the HA-CD44 binding affinity and induced CD44 clustering by HA-based NPs were HA MW-dependent,the two of which determine the apparent targeting efficacy of Dox/HCV NPs in the conflicting directions. Those results laid a good foundation for rationally designing HA-based NPs in cancer therapy.
基金Funded by the National Natural Science Foundation of China(Nos.51473130 and 51572206)the Wuhan Huanghe Excellence Plan and Entrepreneurship Training Program of Wuhan University and Technology(Nos.20171049720018,20171049720019 and 20171049720009)
文摘This work aimed to develop an intelligent multi-target tracking hyaluronic acid-RGDchlorambucil-quantum dots（HA-RGD-CLB-QDs） drug delivery system. After deacetylated, hyaluronic acid was reacted with anticancer drug chlorambucil, RGD, and quantum dots to obtain the HA-RGD-CLB-QDs drug delivery system. The characterization by FT-IR, ~1 H NMR, TEM, XPS, DLS, and UV-vis absorption and fluorescence spectra show that the system is successfully constructed with an average particle size of about 70 nm. The results of the drug release profile show that that the system has a p H and enzyme sensitive controlled release behaviour. Moreover, cellular uptake and toxicity results show that the system has an ideal dual receptormediated endocytosis pathway that significantly enhances the efficacy of CLB tumor therapy and has a lower toxicity to normal cells.The system shows the potential application as a carrier for cancer therapy.
基金Supported by the National Natural Science Foundation of China (Grant No. 30500487 and 30700792)
文摘Kupffer cells, expressing toll-like receptor 4 (TLR4), play a central role in hepatic ischemia/reperfusion (I/R) injury. Hyaluronic acid (HA) fragments, degradative products of high-molecular-weight HA (HMW-HA), acquire the ability to activate immune cells under inflammatory conditions. Here we inves- tigated whether HA fragments could activate Kupffer cells and analyzed the underlying mechanism. Kupffer cells were isolated from wild-type mice (WT, C3H/HeN) and TLR4 mutant mice (C3H/HeJ) and HA fragments were produced by the methods of enzyme digestion and chromatography. Then Kupffer cells were stimulated by HA fragments or other control stimuli. The activation of Kupffer cells was estimated as the release of pro-inflammatory cytokines. The activation of p38 MAPK pathway of Kupffer cells was checked and blocking experiments were done as well. The results indicated that HA fragments acquired the ability to activate Kupffer cells in vitro, which was TLR4 dependent and not due to contamination of lipopolysaccharide. Experiments of p38 MAPK kinase inhibition by SB-203580 verified p38 MAPK was required in HA fragments induced Kupffer cells activation. This suggests that HA fragments, degradative products of one of the major glycosaminoglycans of the extracellular matrix, play critical roles in Kupffer cell activation mediated by TLR4 signaling pathway, which is, at least partially, de- pendent on p38 MAPK activation.
