Abstract
Cationic polymers are promising components of the versatile platform of non-viral nucleic acid (NA) delivery agents. For a successful gene delivery system, these NA vehicles need to comprise several functionalities. This work focuses on the modification of oligoaminoamide carriers with hydrophilic oligomer blocks mediating nanoparticle shielding potential, which is necessary to prevent aggregation or dissociation of NA polyplexes in vitro, and hinder opsonization with blood components in vivo. Herein, the shielding agent polyethylene glycol (PEG) in three defined lengths (12, 24, or 48 oxyethylene repeats) is compared with two peptidic shielding blocks composed of four or eight repeats of sequential proline-alanine-serine (PAS). With both types of shielding agents, we found opposing effects of the length of hydrophilic segments on shielding and compaction of formed plasmid DNA (pDNA) nanoparticles. Two-arm oligoaminoamides with 37 cationizable nitrogens linked to 12 oxyethylene units or four PAS repeats resulted in very compact 40–50 nm pDNA nanoparticles, whereas longer shielding molecules destabilize the investigated polyplexes. Thus, the balance between sufficiently shielded but still compact and stable particles can be considered a critical optimization parameter for non-viral nucleic acid vehicles based on hydrophilic-cationic block oligomers.
Highlights
In modern cancer therapy, conventional chemotherapy and surgery often fail [1]
We focused on the effect of the shielding block attached in T-shape topology onto a “two-arm” structure of oligoaminoamide oligomers tailored for plasmid DNA (pDNA) delivery
These findings are in accordance with recent observations [38], where particle morphology changed from long rods to globular condensed polyplexes with decreasing amounts of conjugated polyethylene glycol (PEG)
Summary
Conventional chemotherapy and surgery often fail [1]. with the field of gene therapy, a novel opportunity has reached clinical application [2,3,4]. Much focus has been put on non-viral gene therapy [5,6]. Polymeric vehicles such as linear polyethylenimine (lPEI) with its repetitive diaminoethane motif can address different stages of the delivery pathway in a way similar to viruses [6,7,8]. Stability, and shape of nanoparticles [11,12] play a crucial role for the in vivo biodistribution and survival of nanoparticles, as well as cellular uptake processes [13]. Following cellular uptake by endocytosis, endolysosomal escape of nanoparticles presents a significant bottleneck in the transfection process
Sign-in/Register to view highlights & summary Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
