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 drugresistance 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 qual-ities 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 trypanosomespecific pathway (dual-target approach). The DNAzyme provides a backup to counteract the recovery of compromised parasites, which reduces the risk of developing drug resistance.

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.

Human African trypanosomiasis (HAT) is a neglected tropical disease (NTD) for which adequate therapeutic and diagnostic measures are still lacking. Causative agent of HAT is the African trypanosome, a single-cell parasite, which propagates in the blood and cerebrospinal fluid of infected patients. Although different testing methods for the pathogen exist, none is robust, reliable and cost-efficient enough to support large-scale screening and control programs. Here we propose the design of a new sensor-type for the detection of infective-stage trypanosomes. The sensor exploits the highly selective binding capacity of nucleic acid aptamers to the surface of the parasite in combination with passive sensor structures to allow an electromagnetic remote read-out using terahertz (THz)-radiation. The short wavelength provides a superior interaction with the parasite cells than longer wavelengths, which is essential for a high sensitivity. We present two different sensor structures using both, micro- and nano-scale elements, as well as different measurement principles.

Human African Trypanosomiasis (HAT) is caused by the African trypanosome, a single-cell parasite that proliferates in the blood and cerebrospinal fluid of infected patients. Diagnostic measures for this pathogen are currently not sufficiently robust and reliable enough to permit effective disease control procedures. As a consequence, we suggested the development of a new sensor type, combining the selectivity of parasite-specific nucleic acid aptamers with the sensitivity of resonant electromagnetic devices to capture and detect the disease-causing organism. While we accomplished the detection of parasite cells in dehydrated specimens, here we summarize our recent progress toward electromagnetic sensors capable of uncovering parasites in liquid patient samples. We present a technique for the removal of blood cells from blood specimens and the deposition of trypanosome cells on glass microfiber membranes for dielectric spectrometry. Liquid suspensions of trypanosomes are characterized to determine the actual dielectric properties of single parasites and lastly, we present two sensor concepts optimized for the detection in liquids, along with a fabrication technique for the integration of microfluidic sample confinements.