Optimizing pDNA Lipo-polyplexes: A Balancing Act between Stability and Cargo Release
| Autor: | Elisa Hörterer, Ulrich Wilk, Yanfang Wang, Simone Berger, Teoman Benli-Hoppe, Ernst Wagner, Jie Luo, Özgür Öztürk, Ana Krhac Levacic |
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| Rok vydání: | 2021 |
| Předmět: |
Polymers and Plastics
Endosome Bioengineering 02 engineering and technology Endosomes 010402 general chemistry Transfection 01 natural sciences Biomaterials chemistry.chemical_compound In vivo Gene expression Materials Chemistry Histidine Structural motif Pentamine Gene Transfer Techniques 021001 nanoscience & nanotechnology In vitro 0104 chemical sciences chemistry Lytic cycle Biophysics Nanoparticles Nanocarriers 0210 nano-technology Plasmids |
| Zdroj: | Biomacromolecules. 22(3) |
| ISSN: | 1526-4602 |
| Popis: | When optimizing nanocarriers, structural motifs that are beneficial for the respective type of cargo need to be identified. Here, succinoyl tetraethylene pentamine (Stp)-based lipo-oligoaminoamides (OAAs) were optimized for the delivery of plasmid DNA (pDNA). Structural variations comprised saturated fatty acids with chain lengths between C2 and C18 and terminal cysteines as units promoting nanoparticle stabilization, histidines for endosomal buffering, and disulfide building blocks for redox-sensitive release. Biophysical and tumor cell culture screening established clear-cut relationships between lipo-OAAs and characteristics of the formed pDNA complexes. Based on the optimized alternating Stp-histidine backbones, lipo-OAAs containing fatty acids with chain lengths around C6 to C10 displayed maximum gene transfer with around 500-fold higher gene expression than that of C18 lipo-OAA analogues. Promising lipo-OAAs, however, showed only moderate in vivo efficiency. In vitro testing in 90% full serum, revealing considerable inhibition of lytic and gene-transfer activity, was found as a new screening model predictive for intravenous applications in vivo. |
| Databáze: | OpenAIRE |
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