Well-defined Cationic Shell Crosslinked Nanoparticles for Efficient Delivery of DNA or Peptide Nucleic Acids

Abstract

This mini-review highlights developments that have been made over the past year to advance the construction of well-defined nanoscale objects to serve as devices for cell transfection. Design of the nanoscale objects originated from biomimicry concepts, using histones as the model, to afford cationic shell crosslinked knedellike (cSCK) nanoparticles. Packaging and delivery of plasmid DNA, oligonucleotides, and peptide nucleic acids were studied by dynamic light scattering, transmission electron microscopy, gel electrophoresis, biological activity assays, RT-PCR measurements, flow cytometry, and confocal fluorescence microscopy. With the demonstration of more efficient cell transfection in vitro than that achieved using commercially-available transfection agents, together with the other features offered by the robust nanostructural framework, work continues toward the application of these cSCKs for in vivo molecular recognition of genetic material, for imaging and therapy targeted specifically to pulmonary injury and disease.

Design of polymeric nanoparticles for biomedical delivery applications

“…Most endosomolytic polymers are designed to be bi-functional, by incorporating primary and/or tertiary amines at different ratios. 31–33 Some of these amine groups are involved in electrostatic complexation with negatively-charged drugs while the unbound amine groups become protonated at the acidic pH of the endosomes, which causes influx of protons together with chloride ions and induces osmotic swelling and subsequent disruption of the endosomes, which is known as the “proton sponge effect”. 34 Another suggested mechanism is that these positively-charged polymers might interact with and disrupt the endosomal membrane.…”

“…These nanoparticles were shown to condense nucleic acid materials of different structures and chemistry, protect them against enzymatic digestion and to afford high transfection efficiency. 31–33, 40 Multifunctional SCKs have been also used for theranostic applications. Theranostic nanoparticles “nanotheranostics” involve the use of multifunctional nanoparticles loaded with therapeutic drugs and imaging probes for the combined therapy and diagnosis.…”

Endosomal escape and siRNA delivery with cationic shell crosslinked knedel-like nanoparticles with tunable buffering capacities

“…SCKs are core–shell nanoparticles composed of amphiphilic block copolymers that self assemble in water, followed by selective crosslinking throughout adjacent chains in the hydrophilic shell layer, which allows SCKs to possess structural and kinetic stabilities. Cationic SCKs (cSCKs), with poly(acrylamidoethylamine) (PAEA) comprising the shells for electrostatic interaction with negatively-charged nucleic acids, have emerged as a promising class of nanomaterials for highly efficient transfection of nucleic acids of various structures [32–34]. In this study, a new class of cSCKs was designed by incorporating various amounts of histamines and primary amines (as low- and high-p K a functionalities) into their shells to achieve enhanced cell transfection with reduced toxicity, by absorbing protons at pH values between the physiological and endosomal pH range, resulting in disruption of endosomal membranes.…”

Effect of PEG Architecture on the Hybridization Thermodynamics and Protein Accessibility of PEGylated Oligonucleotides

“…[1] Upon conjugation with PEG,t he pharmacokinetics of the target molecule can oftentimes be greatly enhanced owing to the "stealth" properties of the polymer. [2] Foro ligonucleotide therapeutics,w hich involve antisense DNA, [3] RNAi nterference, [4] and aptamers, [5] PEGylation is particularly important because oligonucleotides exhibit ar ange of specific or non-specific non-hybridization interactions with cell surface receptors or serum components that lead to unwanted hepatic uptake,p oor stability,a nd many side effects including flu-like symptoms and coagulopathy. [6] Va rious types of PEG-oligonucleotide conjugates have been synthesized and studied, with some reaching clinical trials and regulatory approval.…”