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Materials Today Bio · 2025 · IF 10.2

Carrier-free nanoparticles based on natural products trigger dual "synergy and attenuation" for enhanced phototherapy of liver cancer

Xiongqin Wang,Kunhui Sun,Junlin Dong,Yanli Ge,Haifan Liu,Xingyue Jin,Xiao Pei,Ping Wang,Jianbing Jiang,Tiejie Wang,Xuelei Hu,Shuguang Yuan,Bing Wang,Xie-an Yu

Carrier-free nanoparticles have attracted significant interest owing to their exceptional drug-loading efficiency, simple preparation, and good biosafety. Inspired by the synergism and attenuation strategy of natural products, carrier-free nanoparticles were constructed from a compatibility perspective, aiming to carry natural products to tumor sites as nanoparticles to achieve precise anti-cancer effects. Herein, the carrier-free nanoparticles based on gambogic acid and glycyrrhizic acid (GG NPs) were successfully formed via self-assembly. The internally generated "synergism and attenuation" GG NPs could enhance the anti-tumor effect, reduce toxicity to normal cells, and exhibit tumor-targeting capabilities. Further, to explore the role of GG NPs in enhancing phototherapy, the photosensitizer ZnPc 2 was self-assembled with GG NPs to form GGZ NPs. In vitro studies demonstrated that the GGZ NPs significantly improved phototherapecutic efficacy. Compared with ZnPc 2, the photothermal conversion efficiency was increased to 80.8 %, along with a 1.8-fold increase in tumor growth inhibition, and the singlet oxygen yield of GGZ NPs increased by 2-fold. In vivo experiments demonstrated that GGZ NPs exhibit significant liver-targeting ability and could reduce the liver toxicity induced by gambogic acid, as well as decrease the blood biochemical levels of AST and ALT, achieving externally assisted "synergism and attenuation". Hence, carrier-free nanoparticles based on natural products would bring a new treatment modality to the field of precision liver tumor therapy.

CAS / MDL: 1405-86-3 2752-65-0
研究领域: 纳米技术 · 癌症治疗 · 光疗 · 药学科学 · 生物医学工程
✓ 已验证 产品关联 DOI PubMed 高影响因子
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JOURNAL OF PHARMACEUTICAL AND BIOMEDICAL ANALYSIS · 2020 · IF 3.209

Comparison of content-toxicity-activity of six ingenane-type diterpenoids between Euphorbia kansui before and after stir-fried with vinegar by using UFLC-MS/MS, zebrafish embryos and HT-29 cells

Shi-Kang Zhou,Yi Zhang,Yong-Hui Ju,Qiao Zhang,Da Luo,Yu-Dan Cao,Wei-Feng Yao,Yu-Ping Tang,Li Zhang

The dried roots of Euphorbia kansui (EK) are especially beneficial for the treatment of edema, but the severe toxicity limits their clinical applications. Euphorbia kansui stir-fried with vinegar (VEK) is traditionally employed to reduce the toxicity of EK. However, the material basis for the toxicity reduction with effectivity conservation is still unclear. Therefore, in this study, a rapid, sensitive, and reliable ultra-fast liquid chromatography tandem mass spectrometry (UFLC-MS/MS) method was firstly established to simultaneously determine six ingenane-type diterpenoids, i.e. kansuiphorin C (1) , 5- O -benzoyl-20-deoxyingenol (2) , 20-deoxyingenol (3) , 3- O -(2’ E ,4’ E -decadienoyl)-20- O -acetylingenol (4) , 20- O -(2’ E ,4’ Z -decadienoyl)ingenol (5) , and ingenol (6) , in EK and VEK based on the processing conversion. Then, the toxicity evaluation on zebrafish embryos and modulation of the expression of aquaporin-3 (AQP3) proteins in HT-29 cells were employed to investigate the toxicity-activity of six compounds. Chromatographic separation was obtained on Waters BEH RP18 column (2.1 mm × 100 mm, 2.5 μm) with the mobile phase composed of 0.1 % formic acid in acetonitrile and water, respectively. The column temperature was 35 ℃ at a flow rate of 0.4 mL min −1 . Multiple reaction monitoring was conducted in both positive and negative modes for quantitative analysis. The method was then successfully used for the determination of six compounds in EK and VEK. In addition, 1 , 2 , 4 , and 5 had evident cardiotoxicity, intestinal irritation and nutrient absorption disorders on zebrafish larvae, while no in-vivo toxicity was seen for groups given 3 and 6 (LC 50 > 200 μM). Meanwhile, 1 , 2 , 4 , 5 , and 6 significantly increased the expression of AQP3 protein ( p < 0.05) to promote the excretion of water in the colon. This study demonstrated that toxic ingenane-type diterpenoids converted into the less toxic compounds with the same core structure through the breakage of multiple ester bonds in the side chain. At the same time, the laxative effect was retained, providing useful information for the optimization of the process of EK and quality evaluation of other similar toxic Chinese herbal medicines.

CAS / MDL: 154071-48-4 1461-15-0
研究领域: 药理学 · 毒理学 · 分析化学 · 药学
✓ 已验证 产品关联 DOI PubMed 高影响因子
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