{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,7,30]],"date-time":"2025-07-30T16:13:22Z","timestamp":1753892002592,"version":"3.41.2"},"reference-count":50,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2025,6,11]],"date-time":"2025-06-11T00:00:00Z","timestamp":1749600000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Pharmacol."],"abstract":"<jats:sec><jats:title>Introduction<\/jats:title><jats:p>Dihydroartemisinin (DHA) demonstrates potent anti-echinococcal activity. However, its clinical application is constrained by non-specific biodistribution and low bioavailability. To overcome these limitations and enhance hepatic targeting, the DHA was encapsulated in poly (lactic-co-glycolic acid) (PLGA) nanoparticles, and using sodium taurocholate (STC) as the surface modifier, a novel composite nanoparticle designated as DHA-STC-PLGA nanoparticles (DSP nanoparticles).<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>The formulation was optimized using response surface methodology, and its targeting efficiency was confirmed through in-vivo fluorescence imaging. Both in vitro and in vivo studies were conducted to evaluate the therapeutic efficacy and elucidate the underlying mechanisms of DSP nanoparticles in a murine model of cystic echinococcosis.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>The results showed that the optimal preparation conditions of DSP nanoparticles were 40 mg\/mL STC, a DHA\/PLGA1:10, ultrasonic power (UP) of 80, and oil in water (O\/W) ratio was 1:20. Under these conditions, the DSP nanoparticles size were 125.73 \u00b1 1.78 nm, exhibited a sustained release of DHA, and maintained stability for up to 42 days. DSP nanoparticles demonstrated good safety at a dosage of 200 mg\/kg. Additionally, DSP nanoparticles demonstrated effective targeting of the liver and intestines. Therapeutic evaluation in a DSP nanoparticles-treated mouse liver hydatid model revealed that the DSP nanoparticles-H group significantly reduced liver, spleen, and vesicle weights compared to both control and albendazole (ABZ)-treated groups (<jats:italic>P<\/jats:italic> &amp;lt;0.05). Furthermore, the DSP nanoparticles-H group significantly decreased serum levels of aspartate aminotransferase (AST), alanine aminotransferase (ALT), total bilirubin (TBIL), direct bilirubin (DBIL), and alkaline phosphatase (ALP). Additionally, levels of interleukin-6 (IL-6), tumor necrosis factor-alpha (TNF-\u03b1), and interleukin-10 (IL-10) were significantly reduced in both serum and cystic fluid, while interferon-gamma (IFN-\u03b3) levels were markedly increased (<jats:italic>P<\/jats:italic> &amp;lt;0.05). In vitro assays further demonstrated that DSP nanoparticles exert anti-echinococcal effects by compromising the integrity of the cyst wall. Mechanistic results suggest that DSP nanoparticles exert potent anti-echinococcal effects through activation of the Wnt signaling pathway and its key regulatory genes.<\/jats:p><\/jats:sec><jats:sec><jats:title>Discussion<\/jats:title><jats:p>Overall, these findings indicate that DSP nanoparticles represent a promising liver-targeted nanoformulation that not only enhances DHA bioavailability but also offers a potent therapeutic strategy against cystic echinococcosis.<\/jats:p><\/jats:sec>","DOI":"10.3389\/fphar.2025.1600525","type":"journal-article","created":{"date-parts":[[2025,6,11]],"date-time":"2025-06-11T04:10:15Z","timestamp":1749615015000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["Dihydroartemisinin-sodium taurocholate-PLGA nanoparticles: a novel therapeutic approach against cystic echinococcosis"],"prefix":"10.3389","volume":"16","author":[{"given":"Aierpati","family":"Moheteer","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jiang","family":"Zhu","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Dongming","family":"Pang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xue","family":"Rao","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Nijiati","family":"Aini","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kalibixiati","family":"Aimulajiang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Zhenping","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Saifuding","family":"Abula","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Adelijiang","family":"Wusiman","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1965","published-online":{"date-parts":[[2025,6,11]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"65","DOI":"10.33899\/ijvs.2021.128926.1624","article-title":"Perturbation of liver function markers and serum electrolytes associated with Echinococcus granulosus infection in sheep","volume":"36","author":"Ali","year":"2021","journal-title":"Iraqi J. Vet. Sci."},{"key":"B2","doi-asserted-by":"publisher","first-page":"2771","DOI":"10.1242\/jcs.146514","article-title":"The tumor suppressor APC differentially regulates multiple \u03b2-catenins through the function of axin and CKI\u03b1 during C. elegans asymmetric stem cell divisions","volume":"127","author":"Baldwin","year":"2014","journal-title":"J. Cell Sci."},{"key":"B3","doi-asserted-by":"publisher","first-page":"2795","DOI":"10.1039\/d2ra07812k","article-title":"Deep learning for automated size and shape analysis of nanoparticles in scanning electron microscopy","volume":"13","author":"Bals","year":"2023","journal-title":"RSC Adv."},{"key":"B4","doi-asserted-by":"publisher","first-page":"6121","DOI":"10.1093\/emboj\/19.22.6121","article-title":"Pontin52 and Reptin52 function as antagonistic regulators of \u03b2\u2010catenin signalling activity","volume":"19","author":"Bauer","year":"2000","journal-title":"EMBO J."},{"key":"B5","doi-asserted-by":"publisher","first-page":"16561","DOI":"10.1039\/d2ra02307e","article-title":"A mechanoresponsive nano-sized carrier achieves intracellular release of drug on external ultrasound stimulus","volume":"12","author":"Catania","year":"2022","journal-title":"RSC Adv."},{"key":"B6","doi-asserted-by":"publisher","first-page":"2391","DOI":"10.1007\/s11010-023-04857-2","article-title":"BML-281 promotes neuronal differentiation by modulating Wnt\/Ca2+ and Wnt\/PCP signaling pathway","volume":"479","author":"Choi","year":"2024","journal-title":"Mol. Cell. Biochem."},{"key":"B7","doi-asserted-by":"publisher","first-page":"119","DOI":"10.1186\/s12911-018-0694-7","article-title":"Automatic gene annotation using GO terms from cellular component domain","volume":"18","author":"Ding","year":"2018","journal-title":"BMC Med. Inf. Decis. Mak."},{"key":"B8","doi-asserted-by":"publisher","first-page":"25","DOI":"10.12677\/acrpvm.2020.93004","article-title":"Research progress of diagnostic antigens based on echinococcosis granulosus at different stages","volume":"9","author":"Ding","year":"2020","journal-title":"Asian Case Rep. Vet. Med."},{"key":"B9","doi-asserted-by":"publisher","DOI":"10.21203\/rs.2.20164\/v1","article-title":"Transcriptomic analysis of the Echinococcus granulosus protoscolex in the encystation process","author":"Fan","year":"2020","journal-title":"Res. Sq."},{"key":"B10","doi-asserted-by":"publisher","first-page":"108781","DOI":"10.1016\/j.envres.2019.108781","article-title":"Long term impact of surfactants and polymers on the colloidal stability, aggregation and dissolution of silver nanoparticles","volume":"179","author":"Fernando","year":"2019","journal-title":"Environ. Res."},{"key":"B11","doi-asserted-by":"publisher","first-page":"1008274","DOI":"10.3389\/fmicb.2022.1008274","article-title":"Suppressive effect of pseudolaric acid B on Echinococcus multilocularis involving regulation of TGF-\u03b21 signaling in vitro and in vivo","volume":"13","author":"Gao","year":"2022","journal-title":"Front. Microbiol."},{"key":"B12","doi-asserted-by":"publisher","first-page":"8859116","DOI":"10.1155\/2020\/8859116","article-title":"Review on epidemiology and public health significance of hydatidosis","volume":"2020","author":"Gessese","year":"2020","journal-title":"Vet. Med. Int."},{"key":"B13","doi-asserted-by":"publisher","first-page":"222","DOI":"10.1016\/j.ijbiomac.2017.08.176","article-title":"Optimization of angelica sinensis polysaccharide-loaded Poly (lactic-co-glycolicacid) nanoparticles by RSM and its immunological activity in vitro","volume":"107","author":"Gu","year":"2018","journal-title":"Int.J. Biol. Macromol."},{"key":"B14","doi-asserted-by":"publisher","first-page":"1098","DOI":"10.1016\/j.jcis.2024.07.151","article-title":"Dynamic light scattering unveils stochastic degradation in large-pore mesoporous silica nanoparticles","volume":"676","author":"Guerrero-Florez","year":"2024","journal-title":"J. Colloid Interface Sci."},{"volume-title":"First-pass effect. StatPearls","year":"2023","author":"Herman","key":"B15"},{"key":"B16","doi-asserted-by":"publisher","first-page":"115","DOI":"10.1186\/s40249-023-01152-6","article-title":"New clinical application prospects of artemisinin and its derivatives: a scoping review","volume":"12","author":"Huang","year":"2023","journal-title":"Infect. Dis. poverty."},{"key":"B17","doi-asserted-by":"publisher","first-page":"87","DOI":"10.15406\/bbij.2017.05.00133","article-title":"A general overview of response surface methodology","volume":"5","author":"Khuri","year":"2017","journal-title":"BBIJ"},{"key":"B18","doi-asserted-by":"publisher","first-page":"502","DOI":"10.1007\/s11626-024-00860-z","article-title":"The interplay between Wnt signaling pathways and microtubule dynamics","volume":"60","author":"Kikuchi","year":"2024","journal-title":"Vitro Cell. Dev. Biol. - Anim."},{"key":"B19","doi-asserted-by":"publisher","first-page":"2940","DOI":"10.2174\/0113816128275385231027054743","article-title":"Poly (lactic-co-glycolic) Acid (PLGA) nanoparticles and transdermal drug delivery: an overview","volume":"29","author":"Kumar","year":"2023","journal-title":"Curr. Pharm. Des."},{"key":"B20","doi-asserted-by":"publisher","first-page":"2004","DOI":"10.4103\/jcrt.jcrt_140_24","article-title":"Dihydroartemisinin ameliorates skeletal muscle atrophy in the lung cancer cachexia mouse model","volume":"20","author":"Li","year":"2024","journal-title":"J. Cancer Res. Ther."},{"key":"B21","doi-asserted-by":"publisher","first-page":"131142","DOI":"10.1016\/j.jhazmat.2023.131142","article-title":"A biomimetic beetle-like membrane with superoleophilic SiO2-induced oil coalescence on superhydrophilic CuC2O4 nanosheet arrays for effective O\/W emulsion separation","volume":"451","author":"Liu","year":"2023","journal-title":"J. Hazard. Mater."},{"key":"B22","doi-asserted-by":"publisher","first-page":"104177","DOI":"10.1016\/j.ebiom.2022.104177","article-title":"HIV protease inhibitor nelfinavir is a potent drug candidate against echinococcosis by targeting Ddi1-like protein","volume":"82","author":"Liu","year":"2022","journal-title":"EBioMedicine"},{"key":"B23","doi-asserted-by":"publisher","first-page":"107066","DOI":"10.1016\/j.actatropica.2023.107066","article-title":"Effects of protoscoleces excretory-secretory products of Echinococcus granulosus on hepatocyte growth, function, and glucose metabolism","volume":"249","author":"Luo","year":"2024","journal-title":"Acta Trop."},{"key":"B24","doi-asserted-by":"publisher","first-page":"20230714","DOI":"10.1515\/med-2023-0714","article-title":"Vitamin D protects intestines from liver cirrhosis-induced inflammation and oxidative stress by inhibiting the TLR4\/MyD88\/NF-\u03baB signaling pathway","volume":"18","author":"Luo","year":"2023","journal-title":"Open Med."},{"key":"B25","doi-asserted-by":"publisher","first-page":"2402773","DOI":"10.1002\/adhm.202402773","article-title":"Sodium butyrate\u2010loaded microspheres with enhanced bioavailability for targeted treatment of intestinal barrier injury","volume":"14","author":"Lv","year":"2025","journal-title":"Adv. Healthc. Mater."},{"key":"B26","doi-asserted-by":"publisher","first-page":"1140","DOI":"10.1093\/abbs\/gmaa101","article-title":"Dihydroartemisinin induces ER stress-dependent apoptosis of Echinococcus protoscoleces in vitro","volume":"52","author":"Ma","year":"2020","journal-title":"Acta Biochim. Biophys. Sin."},{"key":"B27","doi-asserted-by":"publisher","first-page":"545","DOI":"10.21608\/svuijm.2024.255031.1758","article-title":"The pro-inflammatory cytokine tumor necrosis factor alpha (TNF-\u03b1) in diabetic nephropathy","volume":"7","author":"Mahmoud","year":"2024","journal-title":"SVU-Int. J. Med. Sci."},{"key":"B28","doi-asserted-by":"publisher","first-page":"117672","DOI":"10.1016\/j.trac.2024.117672","article-title":"Nanometrics goes beyond the size: assessment of nanoparticle concentration and encapsulation efficiency in nanocarriers","volume":"174","author":"Marques","year":"2024","journal-title":"Trac. Trend. Anal. Chem."},{"key":"B29","doi-asserted-by":"publisher","first-page":"643","DOI":"10.1016\/s2213-2600(21)00103-x","article-title":"Interleukin-6: obstacles to targeting a complex cytokine in critical illness","volume":"9","author":"McElvaney","year":"2021","journal-title":"Lancet. Res. Med."},{"key":"B30","doi-asserted-by":"publisher","first-page":"241","DOI":"10.18231\/j.ijmr.2022.042","article-title":"Response surface methodology (RSM): an overview to analyze multivariate data","volume":"9","author":"Reji","year":"2022","journal-title":"Indian J. Microbiol. Res."},{"key":"B31","doi-asserted-by":"publisher","first-page":"108042","DOI":"10.1016\/j.exppara.2020.108042","article-title":"Effects of Allium sativum on IFN-\u03b3 and IL4 concentrations in mice with cystic echinococcosis","volume":"220","author":"Shirgholami","year":"2021","journal-title":"Exp. Parasitol."},{"key":"B32","doi-asserted-by":"publisher","first-page":"46","DOI":"10.1186\/s13045-024-01563-4","article-title":"Wnt\/\u03b2-catenin signaling pathway in carcinogenesis and cancer therapy","volume":"17","author":"Song","year":"2024","journal-title":"J. Hematol. Oncol."},{"key":"B33","doi-asserted-by":"publisher","first-page":"107137","DOI":"10.1016\/j.ultsonch.2024.107137","article-title":"Ultrasonication-mediated synthesis of diblock polymer-based nanoparticles for advanced drug delivery systems: insights and optimization","volume":"111","author":"Sreeharsha","year":"2024","journal-title":"Ultrason. Sonochem."},{"key":"B34","doi-asserted-by":"publisher","first-page":"1250","DOI":"10.2174\/0115680096283208231229103822","article-title":"Hybrid Nanoparticle for Co-delivering paclitaxel and dihydroartemisinin to exhibit synergic anticancer therapeutics","volume":"24","author":"Tran","year":"2024","journal-title":"Curr. Cancer Drug Targets."},{"key":"B35","doi-asserted-by":"publisher","first-page":"291","DOI":"10.3347\/kjp.2016.54.3.291","article-title":"Construction of in vivo fluorescent imaging of Echinococcus granulosus in a mouse model","volume":"54","author":"Wang","year":"2016","journal-title":"Korean J. Parasitol."},{"key":"B36","first-page":"552","article-title":"Differential expression of six wnt gene family members in Echinococcus granulosus protoscoleces and adult worms","volume":"34","author":"Wang","year":"2016","journal-title":"Chin. J. Parasitol. Parasit. Dis."},{"key":"B37","doi-asserted-by":"publisher","first-page":"e00075-18","DOI":"10.1128\/cmr.00075-18","article-title":"Echinococcosis: advances in the 21st century","volume":"32","author":"Wen","year":"2019","journal-title":"Clin. Microbiol. Rev."},{"key":"B38","doi-asserted-by":"publisher","first-page":"4685","DOI":"10.2147\/dddt.s254166","article-title":"In vitro and in vivo effects of artesunate on Echinococcus granulosus protoscoleces and metacestodes","volume":"14","author":"Wen","year":"2020","journal-title":"Drug Des. Dev. Ther."},{"key":"B39","doi-asserted-by":"publisher","first-page":"e0047022","DOI":"10.1128\/iai.00470-22","article-title":"Effects of dihydroartemisinin against cystic echinococcosis in vitro and in vivo","volume":"91","author":"Wen","year":"2023","journal-title":"Infect. Immun."},{"key":"B40","doi-asserted-by":"publisher","first-page":"475","DOI":"10.1016\/j.ajps.2022.04.005","article-title":"Development of nanoscale drug delivery systems of dihydroartemisinin for cancer therapy: a review","volume":"17","author":"Wong","year":"2022","journal-title":"Asian J. Pharm. Sci."},{"key":"B41","doi-asserted-by":"publisher","first-page":"130","DOI":"10.1016\/j.ijbiomac.2022.01.020","article-title":"Alhagi honey polysaccharides encapsulated into PLGA nanoparticle-based pickering emulsion as a novel adjuvant to induce strong and long-lasting immune responses","volume":"202","author":"Wusiman","year":"","journal-title":"Int. J. Biol. Macromol."},{"key":"B42","doi-asserted-by":"publisher","first-page":"102112","DOI":"10.1016\/j.psj.2022.102112","article-title":"Preparation and sulfate modified of Lagenaria siceraria (Molina) Standl polysaccharide and its immune-enhancing adjuvant activity","volume":"101","author":"Wusiman","year":"","journal-title":"Poult. Sci."},{"key":"B43","doi-asserted-by":"publisher","first-page":"1993","DOI":"10.1007\/s00436-022-07536-1","article-title":"Expression profiling of exosomal miRNAs derived from different stages of infection in mice infected with Echinococcus granulosus protoscoleces using high-throughput sequencing","volume":"121","author":"Xiao","year":"2022","journal-title":"Parasitol. Res."},{"key":"B44","doi-asserted-by":"publisher","first-page":"848458","DOI":"10.3389\/fvets.2022.848458","article-title":"Transcriptomic profiles of splenic CD19+ B cells in mice chronically infected with the larval Echinococcus granulosus","volume":"9","author":"Xu","year":"2022","journal-title":"Front. Vet. Sci."},{"key":"B45","doi-asserted-by":"publisher","first-page":"BR139","DOI":"10.12659\/msm.881760","article-title":"The inhibitory effect of Zingiber corallinum Hance essential oil on drug-resistant bacteria and evaluation of its acute toxicity","volume":"17","author":"Yang","year":"2011","journal-title":"Med. Sci. Monit."},{"key":"B46","doi-asserted-by":"publisher","first-page":"36","DOI":"10.1080\/15476278.2018.1455010","article-title":"Effect of TAK1 on osteogenic differentiation of mesenchymal stem cells by regulating BMP-2 via Wnt\/\u03b2-catenin and MAPK pathway","volume":"14","author":"Yang","year":"2018","journal-title":"Organogenesis"},{"key":"B47","doi-asserted-by":"publisher","first-page":"2416","DOI":"10.1111\/anu.13373","article-title":"Dietary emulsifier and antioxidant improved astaxanthin utilization and antioxidant capacity of rainbow trout (Oncorhynchus mykiss)","volume":"27","author":"Zhang","year":"2021","journal-title":"Aquacult. Nutr."},{"key":"B48","doi-asserted-by":"publisher","first-page":"e0009927","DOI":"10.1371\/journal.pntd.0009927","article-title":"Synergism therapeutic and immunoregulatory effects of Albendazole+ rAd-mIL-28B against Echinococcosis in experiment-infected mice with protoscoleces","volume":"15","author":"Zhang","year":"2021","journal-title":"PLoS Negl. Trop. Dis."},{"key":"B49","doi-asserted-by":"publisher","first-page":"121665","DOI":"10.1016\/j.ijpharm.2022.121665","article-title":"Design of red blood cell membrane-cloaked dihydroartemisinin nanoparticles with enhanced antimalarial efficacy","volume":"618","author":"Zuo","year":"2022","journal-title":"Int. J. Pharm."},{"key":"B50","doi-asserted-by":"publisher","first-page":"114019","DOI":"10.1016\/j.ecoenv.2022.114019","article-title":"Wnt 5a mediated inflammatory injury of renal tubular epithelial cells dependent on calcium signaling pathway in trichloroethylene sensitized mice","volume":"243","author":"Zuo","year":"2022","journal-title":"Ecotoxicol. Environ. Saf."}],"container-title":["Frontiers in Pharmacology"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fphar.2025.1600525\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,6,11]],"date-time":"2025-06-11T04:10:20Z","timestamp":1749615020000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fphar.2025.1600525\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,6,11]]},"references-count":50,"alternative-id":["10.3389\/fphar.2025.1600525"],"URL":"https:\/\/doi.org\/10.3389\/fphar.2025.1600525","relation":{},"ISSN":["1663-9812"],"issn-type":[{"type":"electronic","value":"1663-9812"}],"subject":[],"published":{"date-parts":[[2025,6,11]]},"article-number":"1600525"}}