EUROPEAN JOURNAL OF PHARMACEUTICAL SCIENCES
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2021
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IF 4.384
Yuping Wei,Caiying Zhang,Man Zhang,Qionghong Niu,Fengli Hui,Zi Liu,Xia Xu
In our previous study, a novel cell penetrating peptide (CPP) R7 (Arg-Arg-Arg-Arg-Arg-Trp-Trp, RRRRRWW) has been developed to help cellular internalization of paclitaxel (PTX) through the non-covalent interaction with CPP. However, the facilitation mechanism of R7 mediated PTX translocation is not clear. Here the uptake pathways of R7 and R7-PTX were investigated by in vitro test and molecular simulations. In vitro experiments reveal that both R7 and R7-PTX complex translocate through the direct translocation and clathrin mediated endocytosis and associate with the macropinocytosis pathway at high CPP concentration. The translocation of R7(0.1 mM)-PTX complex further involves the lipid raft/caveolae mediated endocytosis. The simulation results show that the synergistic effect between R7 and PTX not only changes the penetration energy barrier but also activates the macropinocytosis and lipid raft/caveolae mediated pathway, resulting in the improvement in the translocation. The presence of heparin also improves the R7 and R7-PTX translocation. These studies provide a theoretical basis for understanding PTX delivery facilitated by the synergistic effect between CPP and cargo and paves a way for CPP design.
研究领域:
药学
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分子生物学
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细胞生物学
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生物物理学
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药物递送系统
✓ 已验证
产品关联
DOI
PubMed
高影响因子
JOURNAL OF DRUG DELIVERY SCIENCE AND TECHNOLOGY
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2018
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IF 2.297
Yunzhi Yin,Yiyue Wang,Jun Zhang,Jing Li,Jingjing Chen,Qi Shen
Docetaxel (DTX) is one kind of well-known anticancer drugs against tumors. GDC0941 was used to inhibit PI3K/Akt signal pathway and improve anti-tumor activity. PLGA-PEG-R7 (poly lactic-co-glycolic acid polyethylene glycol bending with cell penetrating peptide R7)/poly sulfadimethoxine-Folate nanoparticles (R7/PSD-Fol NPs) were made to load DTX and GDC0941 simultaneously. In vitro, the release capacity of DTX and GDC0941 inside nanoparticles was determined and both drugs could release from nanoparticles to 70% within 48h. The result of flow cytometry showed that GDC0941 had no interference on cell uptake and R7/PSD-Fol NPs could enhance MCF-7 cells uptake the most significantly. In cell colony study, GDC0941 could further improve the anti-tumor effect of DTX and inhibit the formation of cell clones on the basis of enhancing the uptake of R7/PSD-Fol NPs. The capability of cell colony formation was as follows: DTX > DTX + GDC0941 > R7 NPs > R7/PSD-Fol NPs. The expression of cell apoptosis proteins treated with R7/PSD-Fol NPs was the lowest. The addition of GDC0941 could decrease the full-length content of apoptotic proteins caspase-3 and caspase-9. In vivo, pharmacokinetic parameters results showed us that GDC0941 had no interference on pharmacokinetic study. Main pharmacokinetic parameters of DTX suspension and R7/PSD-Folate NPs suspension showed significant differences.
研究领域:
肿瘤学
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药理学
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纳米技术
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细胞生物学
✓ 已验证
产品关联
DOI
高影响因子
AQUACULTURE
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2022
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IF 5.135
Xulu Chang,Meiru Kang,Lili Yun,Yihao Shen,Junchang Feng,Guokun Yang,Jianxin Zhang,Xiaolin Meng
Host-derived probiotics are widely used in aquaculture because they are able to adapt to the host intestinal environment more easily than other probiotics. However, decreased numbers and activity of live probiotics that occur during processing, storage, transportation, and consumption hinders the increased use of probiotics. In this study, the ability of sodium gluconate to promote the growth of Bacillus velezensis R7–1003, isolated from the intestinal tract of the common carp , was evaluated in vivo. The actions of dietary supplementation with B. velezensis R7–1003 and/or sodium gluconate were investigated in the common carp with respect to growth, the morphology of the intestine, digestive and immune functions, and antioxidant capacity, as well as intestinal microbiota. The results revealed that the addition of 0.3 and 0.6% sodium gluconate to the diet increased B. velezensis R7–1003 growth in the intestinal tract of the common carp. Furthermore, 0.6% sodium gluconate exhibited better results than 0.3%. A diet with host–derived B. velezensis R7–1003 supplementation improved the growth performance of the fish. It also increased the length of the intestinal villi and tight junction gene expression levels, including claudin-2, occludin , and ZO-1 . Host–derived B. velezensis R7–1003 supplementation enhanced the activities of protease, α-amylase, lipase , alkaline phosphatase , acid phosphatase , lysozyme , catalase , glutathione peroxidase , decreased the level of MDA, increased the level of the anti-inflammatory cytokine TGF-β, and decreased the level of the pro-inflammatory cytokine TNF-α. Furthermore, B. velezensis R7–1003 increased the levels of several probiotics, including Lactobacillus and Lactococcus , and bacteria that produce short-chain fatty acids, including Faecalibacterium , Bacteroides , and Clostridium . The ratio of Firmicutes/Bacteroidetes was reduced in the intestine of the common carp. Importantly, this study indicated that the combination of B. velezensis R7–1003 and sodium gluconate provided additional beneficial effects to the common carp. Thus, this study demonstrated that sodium gluconate promoted B. velezensis R7–1003 growth, which increased the growth performance and intestinal health of the common carp. The results indicated that further study is warranted concerning the use of B. velezensis R7–1003 combined with sodium gluconate as a diet supplement in other economically viable fish.
研究领域:
水产养殖
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微生物学
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营养学
✓ 已验证
产品关联
DOI
高影响因子
MOLECULAR PHARMACEUTICS
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2017
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IF 4.44
Yiyue Wang,Jing Li,Jing Jing Chen,Xuan Gao,Zun Huang,Qi Shen
The polylactic-co-glycolic acid polyethylene glycol conjugated with cell penetrating peptide R7 (PLGA–PEG-R7)/polysulfadimethoxine-folate nanoparticles loaded with docetaxel (DTX) and GDC0941 (R7/PSD-Fol NPs) were prepared to overcome multidrug resistance (MDR) and enhance the antitumor activity. First, polysulfadimethoxine-folate was synthesized to construct the R7/PSD-Fol NPs. The R7/PSD-Fol NPs were prepared with the abilities of effective entrapment and drug loading. Due to the pH-sensitive effect of PSD-folate, the releasing of DTX and GDC0941 from the R7/PSD-Fol NPs was lower in pH 7.4 buffer solution than that in pH 5.0 buffer solution. The half maximal inhibitory concentration (IC50) of MCF-7 and resistant to doxorubicin (MCF-7/Adr) cells illustrated the cytotoxicity of R7/PSD-Fol nanoparticles by using the MTT method. The uptake of R7/PSD-Fol NPs was visualized by using the fluorescence of Rh-123 to detect the targeting effect of folate on the surface of R7/PSD-Fol NPs. The results of the cell apoptosis and the depolarization of mitochondrial membrane potential (MMP) were adopted to show the cytotoxicity of the R7/PSD-Fol NPs on MCF-7/Adr cells. The Western blot revealed the inhibition of PI3K/Akt pathway in MCF-7/Adr cells induced by R7/PSD-Fol NPs. Finally, both in vivo distribution and in vivo antitumor showed the R7/PSD-Fol NPs displayed the better distribution at tumor site and the stronger suppression of tumor growth in the tumor bearing nude mice compared with control group. It was concluded that R7/PSD-Fol NPs loaded with DTX and GDC0941 could overcome MDR and enhance the antitumor effect further.
研究领域:
药理学
·
肿瘤学
·
纳米技术
·
分子生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
危险品化学品经营许可证（带存储）