Lipids in Health and Disease
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2024
·Vol. 23
·期 1
·1-12
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IF 3.9
Fan Yibao,Zhang Wei,Iqbal Zoya,Li Xinxin,Lin Zhiyin,Wu Zhuolin,Li Qianyou,Dong Hongxia,Zhang Xianbin,Gong Peng,Liu Peng
Background Bufalin (BA) is a potent traditional Chinese medicine derived from toad venom. It has shown significant antitumor activity, but its use is limited by cardiotoxicity, which necessitates innovative delivery methods, such as rod-shaped mesoporous silica nanoparticles (rMSNs). rMSNs have been extensively employed for reducing drug toxicity and for controlled or targeted drug delivery in tumor therapy. However, their potential in delivering BA has not been completely elucidated. Therefore, in this study, BA-loaded rMSNs (BA-rMSNs) were developed to investigate their potential and mechanism in impairing colon cancer cells.Methods rMSNs were developed via the sol‒gel method. Drug encapsulation efficiency and loading capacity were determined to investigate the advantages of the rMSN in loading BA. The antiproliferative activities of the BA-rMSNs were investigated via 5-ethynyl-2’-deoxyuridine and CCK-8. To evaluate cell death, Annexin V-APC/PI apoptotic and calcein-AM/PI double staining were performed. Western blotting, oil red O staining, and Nile red solution were employed to determine the ability of BA-rMSNs to regulate lipophagy.Results The diameter of the BA-rMSNs was approximately 60 nm. In vitro studies demonstrated that BA-rMSNs markedly inhibited HCT 116 and HT-29 cell proliferation and induced cell death. In vivo studies revealed that BA-rMSNs reduced BA-mediated cardiotoxicity and enhanced BA tumor targeting. Mechanistic studies revealed that BA-rMSNs blocked lipophagy.Conclusion srMSNs reduced BA-mediated cardiotoxicity and impaired the growth of colon cancer cells. Mechanistically, antitumor activity depends on lipophagy.
研究领域:
药学
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纳米技术
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肿瘤学
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分子生物学
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DOI
PubMed
高影响因子
INTERNATIONAL JOURNAL OF MOLECULAR MEDICINE
·
2020
·Vol. 46
·期 6
·2137-2149
·
IF 3.098
Lijia Pan,Litong Nie,Sheng Yao,Aiwei Bi,Yang Ye,Yeming Wu,Zhen Tan,Zhixiang Wu
The prognosis of high‑risk neuroblastoma remains poor. Clinical first‑line drugs for treating neuroblastoma have been developed over the previous half‑century; however, progress in the identification of new drugs with high efficiency is required. Bufalin, one of the major components of extracts obtained from the venom of the Chinese toad Bufo gargarizans, which is used to treat heart failure in Asian Pacific countries, has been reported to be a potential drug against multiple types of tumor; however, the detailed mechanisms underlying its antitumor activities remain unclear, largely due to lack of knowledge regarding its targets. In the present study, bufalin was revealed to exhibit potent antitumor effects against neuroblastoma, both in vitro and in vivo, using cell proliferation, colony formation, Transwell migration and flow cytometry assays, as well as a nude mouse subcutaneous xenograft model. Moreover, a chemically modified bufalin probe was designed to identify the potential targets of bufalin in neuroblastoma via chemical proteomics. With this strategy, it was revealed that the electron transport chain (ETC) on the inner membrane of mitochondria may contain potential targets for bufalin, and that bufalin‑induced mitochondrial‑dependent apoptosis may be caused by disruption of the ETC. Collectively, the present study suggests that bufalin may a promising drug for chemotherapy against neuroblastoma, and provides a foundation for further studies into the antitumor mechanisms of bufalin.
研究领域:
肿瘤学
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药理学
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细胞生物学
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化学蛋白质组学
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DOI
PubMed
高影响因子
Nanomedicine
·
2024
·
IF 4.7
Yi Wu,Jiahui Tian,Jialu Yang,Qian Peng,Zhengchun Wu,Rushi Liu,Mengjie Luo,Yilan Qiu,Ruiyun Cao
Purpose: We constructed biomimetic nanoparticles with biocompatible, tumor-targeting, laser-responsive properties for ferroptosis-induced colorectal cancer chemo-photothermal therapy, with the aim to realize double-hit ferroptosis treatment for colorectal cancer. Methods: The nanoparticles were prepared by first loading the chemotherapy drug bufotalin (CS-5) with Prussian blue (PB), then combining a hybridized erythrocyte–tumor membrane (M) with PB@CS-5 to produce PB@CS-5@M. The chemo-photothermal therapy efficiency of PB@CS-5@M was tested by in vitro and in vivo experiments. Results and conclusion: The combined PB and CS-5 act as promising ferroptosis inducers to enhance ferroptosis efficacy. The hyperthermia induced by laser stimulation can trigger PB to release CS-5 and iron and ferrous ions, which further promotes ferroptosis.
研究领域:
纳米技术
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肿瘤学
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药学
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生物医学工程
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DOI
PubMed
高影响因子
MICROCHEMICAL JOURNAL
·
2020
·
IF 3.594
Jinghui Zhang,Hongye Pan,Yang Chen,Zafar Iqbal Tanveer,Li Liu,Zongwei Cai,Yanjun Hong,Yongjiang Wu
Natural medicines are now gaining increasing acceptance around the global scope. Due to the complexity of composition , it is imperative to adopt a unique evaluation system, which is not confined to the content of finite marker compounds. This research presents the successful application of pharmacodynamics-based optimization to the ultrasound-assisted extraction of Chansu, a widely used natural medicine with complex bioactive ingredients. The effect of solvent concentration, solvent to solid ratio, extraction time and particle size, on two response indexes (extraction yield of total content of bufalin , cinobufagin and resibufogenin and anticancer activity) were evaluated by response surface methodology (RSM). Two models were built based on two response indexes, and both of them provided accurate predictions. Compared with extraction yield-based optimization, pharmacodynamics-based optimization aligns well with the integrity and complexity of natural medicines. Moreover, the pharmacodynamics-based optimization gives a more economical and efficient optimal condition, which is specifically embodied in the coarser requirement for particle size and the saving of extraction time and solvent. The recommended extraction conditions were methanol concentration of 83.54% (v/v), solvent to solid ratio of 26.23 mL/g, extraction time of 40.43 min and particle size of 61 mesh (0.212–0.25 mm). The present study elaborated the feasibility and implication of pharmacodynamics-based optimization, which provides useful information for further research on the extraction process of natural medicines.
研究领域:
药理学
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药物化学
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生物技术
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产品关联
DOI
高影响因子