{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,26]],"date-time":"2026-02-26T15:02:09Z","timestamp":1772118129888,"version":"3.50.1"},"reference-count":60,"publisher":"Wiley","issue":"20","license":[{"start":{"date-parts":[[2022,9,20]],"date-time":"2022-09-20T00:00:00Z","timestamp":1663632000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"content-domain":{"domain":["chemistry-europe.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["ChemBioChem"],"published-print":{"date-parts":[[2022,10,19]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>\n                    <jats:italic>Trypanosoma brucei<\/jats:italic>\n                    is the causal infectious agent of African trypanosomiasis in humans and Nagana in livestock. Both diseases are currently treated with a small number of chemotherapeutics, which are hampered by a variety of limitations reaching from efficacy and toxicity complications to drug\u2010resistance problems. Here, we explore the forward design of a new class of synthetic trypanocides based on nanostructured, core\u2010shell DNA\u2010lipid particles. In aqueous solution, the particles self\u2010assemble into micelle\u2010type structures consisting of a solvent\u2010exposed, hydrophilic DNA shell and a hydrophobic lipid core. DNA\u2010lipid nanoparticles have membrane\u2010adhesive qualities and can permeabilize lipid membranes. We report the synthesis of DNA\u2010cholesterol nanoparticles, which specifically subvert the membrane integrity of the\n                    <jats:italic>T. brucei<\/jats:italic>\n                    lysosome, killing the parasite with nanomolar potencies. Furthermore, we provide an example of the programmability of the nanoparticles. By functionalizing the DNA shell with a spliced leader (SL)\u2010RNA\u2010specific DNAzyme, we target a second trypanosome\u2010specific pathway (dual\u2010target approach). The DNAzyme provides a backup to counteract the recovery of compromised parasites, which reduces the risk of developing drug resistance.\n                  <\/jats:p>","DOI":"10.1002\/cbic.202200410","type":"journal-article","created":{"date-parts":[[2022,8,30]],"date-time":"2022-08-30T11:43:46Z","timestamp":1661859826000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["Core\u2010Shell DNA\u2010Cholesterol Nanoparticles Exert Lysosomolytic Activity in African Trypanosomes**"],"prefix":"10.1002","volume":"23","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-1483-8579","authenticated-orcid":false,"given":"Robert","family":"Knie\u00df","sequence":"first","affiliation":[{"name":"Molecular Genetics Technical University Darmstadt  Schnittspahnstr. 10 64287 Darmstadt Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5258-1255","authenticated-orcid":false,"given":"Wolf\u2010Matthias","family":"Leeder","sequence":"additional","affiliation":[{"name":"Molecular Genetics Technical University Darmstadt  Schnittspahnstr. 10 64287 Darmstadt Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Paul","family":"Rei\u00dfig","sequence":"additional","affiliation":[{"name":"Molecular Genetics Technical University Darmstadt  Schnittspahnstr. 10 64287 Darmstadt Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Felix Klaus","family":"Geyer","sequence":"additional","affiliation":[{"name":"Molecular Genetics Technical University Darmstadt  Schnittspahnstr. 10 64287 Darmstadt Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2353-2822","authenticated-orcid":false,"given":"H. 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