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Core‐Shell DNA‐Cholesterol Nanoparticles Exert Lysosomolytic Activity in African Trypanosomes

Knieß, Robert ; Leeder, Wolf‐Matthias ; Reißig, Paul ; Geyer, Felix Klaus ; Göringer, H. Ulrich (2023)
Core‐Shell DNA‐Cholesterol Nanoparticles Exert Lysosomolytic Activity in African Trypanosomes.
In: ChemBioChem, 2022, 23 (20)
doi: 10.26083/tuprints-00022889
Artikel, Zweitveröffentlichung, Verlagsversion

Es ist eine neuere Version dieses Eintrags verfügbar.

URL / URN: https://tuprints.ulb.tu-darmstadt.de/22889

Kurzbeschreibung (Abstract)

Trypanosoma brucei 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‐resistance problems. Here, we explore the forward design of a new class of synthetic trypanocides based on nanostructured, core‐shell DNA‐lipid particles. In aqueous solution, the particles self‐assemble into micelle‐type structures consisting of a solvent‐exposed, hydrophilic DNA shell and a hydrophobic lipid core. DNA‐lipid nanoparticles have membrane‐adhesive qualities and can permeabilize lipid membranes. We report the synthesis of DNA‐cholesterol nanoparticles, which specifically subvert the membrane integrity of the T. brucei 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)‐RNA‐specific DNAzyme, we target a second trypanosome‐specific pathway (dual‐target approach). The DNAzyme provides a backup to counteract the recovery of compromised parasites, which reduces the risk of developing drug resistance.

Typ des Eintrags:

Artikel

Erschienen:

2023

Autor(en):

Knieß, Robert ; Leeder, Wolf‐Matthias ; Reißig, Paul ; Geyer, Felix Klaus ; Göringer, H. Ulrich

Art des Eintrags:

Zweitveröffentlichung

Titel:

Core‐Shell DNA‐Cholesterol Nanoparticles Exert Lysosomolytic Activity in African Trypanosomes

Sprache:

Englisch

Publikationsjahr:

27 November 2023

Ort:

Darmstadt

Publikationsdatum der Erstveröffentlichung:

2022

Ort der Erstveröffentlichung:

Weinheim

Verlag:

Wiley-VCH

Titel der Zeitschrift, Zeitung oder Schriftenreihe:

ChemBioChem

Jahrgang/Volume einer Zeitschrift:

(Heft-)Nummer:

Kollation:

10 Seiten

DOI:

10.26083/tuprints-00022889

URL / URN:

https://tuprints.ulb.tu-darmstadt.de/22889

Zugehörige Links:

Verlags-DOI

Herkunft:

Zweitveröffentlichung DeepGreen

Kurzbeschreibung (Abstract):

Alternatives oder übersetztes Abstract:

Alternatives Abstract

Sprache

The bioengineering of synthetic nanoparticles with therapeutic potential for the treatment of African sleeping sickness is reported. The molecules are DNA-cholesterol amphiphiles, which self-assemble into micelle-type nanoparticles with an exterior DNA shell and a lipid core. The particles are constructed to attack two parasite-specific targets thereby reducing the risk of developing drug resistance.

Englisch

Freie Schlagworte:

African trypanosomes, chemotherapeutics, DNAzymes, DNA nanoparticles, drug design

ID-Nummer:

e202200410

Status:

Verlagsversion

URN:

urn:nbn:de:tuda-tuprints-228897

Zusätzliche Informationen:

A previous version of this manuscript has been deposited on a preprint server (https://doi.org/10.1101/2022.07.18.500428).

Sachgruppe der Dewey Dezimalklassifikatin (DDC):