INTERNATIONAL JOURNAL OF BIOLOGICAL MACROMOLECULES
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2022
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IF 8.025
Jianshuang Jiao,Juan Yu,Haiyu Ji,Anjun Liu
In the present study, the previously obtained macromolecuar-weight Astragalus polysaccharide (average molecular weight of 1.61 × 10 6 Da) was used as a stabilizer and dispersing agent for nano-composites preparation by modifying selenium nanoparticles, and then the anti-hepatoma activity on HepG2 cells was investigated as well. Results showed that the nano-composites were obtained under polysaccharide concentration of 2 mg/mL and selenium/polysaccharide mass ratio of 1:15, and exhibited symmetrical spheroid with an average diameter of 62.3 nm, which has a good stability for 35 days at 4 °C. Furthermore, the in vitro anti-hepatoma experiments demonstrated that the composites could significantly inhibit the proliferation of HepG2 cells in a dose-dependent manner, and could induce the morphological changes, arrest the cell cycle in S phase, finally triggering HepG2 cells apoptosis through mitochondrial pathway. These data revealed that the composites had the potential to be a novel therapeutic drug or adjuvant for hepatoma-bearing patient treatments.
研究领域:
药学
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癌症生物学
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纳米技术
✓ 已验证
产品关联
DOI
PubMed
高影响因子
MOLECULAR PHARMACEUTICS
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2021
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IF 4.939
Li Wu,Yan Shi,Zihui Ni,Tao Yu,Zhipeng Chen
Mitochondria are involved in the regulation of apoptosis, making them a promising target for the development of new anticancer drugs. Doxorubicin (DOX), a chemotherapeutic drug, can induce reactive oxygen species (ROS)-mediated apoptosis, improving its anticancer effects. Herein, Rhein, an active ingredient in rhubarb, with the capability of self-assembly and mitochondrial targeting, was used in conjunction with DOX to form efficient nanomaterials (Rhein–DOX nanogel) capable of sustained drug release. It was self-assembled with a hydrogen bond, π–π stacking interactions, and hydrophobic interactions as the main driving force, and its loading efficiency was up to 100%. Based on its self-assembly characteristics, we evaluated the mechanism of this material to target mitochondria, induce ROS production, and promote apoptosis. The IC50 of the Rhein–DOX nanogel (3.74 μM) was only 46.3% of that of DOX (11.89 μM), and the tumor inhibition rate of the Rhein–DOX nanogel was 79.4% in vivo, 2.3 times that of DOX. This study not only addresses the disadvantages of high toxicity of DOX and low bioavailability of Rhein, when DOX and Rhein are combined for the treatment of hepatoma, but it also significantly improved the synergistic antihepatoma efficacy of Rhein and DOX, which provides a new idea for the development of long-term antihepatoma agents with low toxicity.
研究领域:
药学
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癌症研究
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纳米技术
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分子生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
International Journal of Nanomedicine
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2024
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IF 6.6
Yunyan Chen,Ziwei Zhang,Zhilei Qian,Rui Ma,Minna Luan,Yu Sun
Background A sequential release co-delivery system is an effective strategy to improve anti-cancer efficacy. Herein, multicomponent-based liposomes (TET-CTM/L) loaded with tetrandrine (TET) and celastrol (CEL)-loaded coix seed oil microemulsion (CTM) were fabricated, which showed synergistic anti-liver cancer activities. By virtue of Enhanced Permeability and Retention (EPR) effect, TET-CTM/L can achieve efficient accumulation at the tumor site. TET was released initially to repair abnormal vessels and decrease the fibroblasts, and CTM was released subsequently for eradication of tumor tissue.Methods TEM (transmission electron microscopy) and DLS (dynamic light scattering) were adopted to characterize the TET-CTM/L. Flow cytometry was adopted to examine the cellular uptake and cytotoxicity of HepG2 cells. The HepG2 xenograft nude mice were adopted to evaluate the anti-tumor efficacy and systemic safety of TET-CTM/L.Results TEM images of TET-CTM/L showed the structure of small particle size of CTM within large-size liposomes, indicating that CTM can be encapsulated in liposomes by film dispersion method. In in vitro studies, TET-CTM/L induced massive apoptosis toward HepG2 cells, indicating synergistic cytotoxicity against HepG2 cells. In in vivo studies, TET-CTM/L displayed diminished systemic toxicity compared to celastrol or TET used alone. TET-CTM/L showed the excellent potential for tumor-targeting ability in a biodistribution study.Conclusion Our study provides a new strategy for combining anti-cancer therapy that has good potential not only in the treatment of liver cancer but also can be applied to the treatment of other solid tumors.
研究领域:
药学
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肿瘤学
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纳米技术
✓ 已验证
产品关联
DOI
PubMed
高影响因子
JOURNAL OF AGRICULTURAL AND FOOD CHEMISTRY
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2024
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IF 5.7
Biao Ma,Sai Shi,Wei Guo,Hailin Zhang,Zhen Zhao,Hailong An
Plant metabolites from natural product extracts offer unique advantages against carcinogenesis in the development of drugs. The target-based virtual screening from food-derived compounds represents a promising approach for tumor therapy. In this study, we performed virtual screening to target the presumed inhibitor-binding pocket and identified a highly potent Kv10.1 inhibitor, liensinine (Lien), which can inhibit the channel in a dose-dependent way with an IC50 of 0.24 ± 0.07 μM. Combining molecular dynamics simulations with mutagenesis experiments, our data show that Lien interacts with Kv10.1 by binding with Y539, T543, D551, E553, and H601 in the C-linker domain of Kv10.1. In addition, the interaction of sequence alignment and 3D structural modeling revealed differences between the C-linker domain of the Kv10.1 channel and the Kv11.1 channel. Furthermore, antitumor experiments revealed that Lien suppresses the proliferation and migration of HCC both in vitro and in vivo. In summary, the food-derived compound, Lien, may serve as a lead compound for antihepatoma therapeutic drugs targeting Kv10.1.
研究领域:
药理学
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肿瘤学
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分子生物学
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药物发现
✓ 已验证
产品关联
DOI
PubMed
高影响因子
DRUG DELIVERY
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2022
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IF 6.819
Dongliang Cheng,Zhiwei Wen,Hui Chen,Shiyuan Lin,Wei Zhang,Xin Tang,Wei Wu
To increase the antitumor drug concentration in the liver tumor site and improve the therapeutic effects, a functionalized liposome (PPP-LIP) with tumor targetability and enhanced internalization after matrix metalloproteinase-2 (MMP2)-triggered cell-penetrating peptide (TATp) exposure was modified with myrcludex B (a synthetic HBV preS-derived lipopeptide endowed with compelling liver tropism) for liver tumor-specific delivery. After intravenous administration, PPP-LIP was mediated by myrcludex B to reach the hepatocyte surface. The MMP2-overexpressing tumor microenvironment deprotected PEG, exposing it to TATp, facilitating tumor penetration and subsequent efficient destruction of tumor cells. In live imaging of small animals and cellular uptake, PPP-LIP was taken up much more than typical unmodified liposomes in the ICR mouse liver and liver tumor cells. Hydroxycamptothecin (HCPT)-loaded PPP-LIP showed a better antitumor effect than commercially available HCPT injections among MTT, three-dimensional (3 D) tumor ball, and tumor-bearing nude mouse experiments. Our findings indicated that PPP-LIP nanocarriers could be a promising tumor-targeted medication delivery strategy for treating liver cancers with elevated MMP2 expression.
研究领域:
药理学
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肿瘤学
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纳米技术
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药物递送系统
✓ 已验证
产品关联
DOI
PubMed
高影响因子
INTERNATIONAL JOURNAL OF BIOLOGICAL MACROMOLECULES
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2024
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IF 7.7
Shaojie Zhang,Renjie Gao,Baocong Ding,Junhao Li,Tanggan Wang,Jiaheng Chen,Chong Li,Yukun Jiao,Lijun Song
Combining selenium nanoparticles (SeNPs) with bioactive polysaccharides is one of the effective ways to overcome the shortcomings of SeNPs and polysaccharide and obtain novel antitumor drug candidates. In this study, a heteropolysaccharide (MTP70) with moderate antihepatoma activity was isolated from the stems of Marsdenia tenacissima (Roxb.) Wight et Arn. To further improve the antihepatoma activity of MTP70 and the application of SeNPs, a novel stable nanoparticle (MTP-SeNP) was designed and fabricated. MTP-SeNPs (Se content of 8.25 %) were characterized as monodisperse spherical nanoparticles (50 nm) with MTP70 wrapped on the surface of the SeNPs by the formation of C O⋯Se bonds and possessed high stability and good dispersion in water for almost a month. In addition, MTP-SeNPs showed higher inhibitory effect compared with MTP70. MTP-SeNPs could effectively inhibit the proliferation, invasion, and metastasis of HePG2 cells by inducing apoptosis and arresting the cell cycle at the S phase, which were closely related to the activation of the Bax/Bcl-2/Caspases and p-21/Akt/Cyclin A2 signaling pathways. Our results provide a theoretical basis for further development and application of M. tenacissima polysaccharide, and show that MTP-SeNPs could be explored as a promising anti-hepatoma agent in the pharmaceutical and biomedical industries.
研究领域:
药理学
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纳米技术
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肿瘤学
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细胞生物学
✓ 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）