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Understanding the Interaction of Nanoparticles at the Cellular Interface
Published in D. Sakthi Kumar, Aswathy Ravindran Girija, Bionanotechnology in Cancer, 2023
Cationic polymers’ ability to form polyplexes by incorporating nucleic acids by electrostatic interactions has been a significant area of research from the past years. It is possible to have high transfection rates using cationic polymers with a buffering capacity under the physiological pH. A hypothesis by Boussif et al. stated that any change in osmolarity would lead to swelling and disruption of endosomes [64]. Later, it was identified as the process called the proton sponge effect. In this effect, vacuolar ATPases pump proton into the endosome, leading to protons’ accumulation. Parallelly, protonation leads to the influx of chloride ions and water results in the increased ionic concentration inside the endosome. This osmotic swelling can disrupt endosomes [65]. There is an evidence that highly branched polymers, such as glycogen or polyethyleneimine (PEI), can induce the proton sponge effect if they are immobilized on NPs [66]. Though the proton sponge mechanism is highly debated, it is one of the most widely accepted phenomena for endosomal escape [67]. Charge reversal by polymeric NPs on exposure to pH is another way to escape endosomes using the proton sponge effect [68].
Nanoparticles for Cardiovascular Medicine: Trends in Myocardial Infarction Therapy
Published in Harishkumar Madhyastha, Durgesh Nandini Chauhan, Nanopharmaceuticals in Regenerative Medicine, 2022
Nanoparticles assembled from repetitively branched polymers, with symmetrical ‘tree-like’ branches originating from a core node and spherical 3D morphology, are termed dendrimers. The numerous branches of dendrimers can facilitate a high degree of functionalisation. The multitude of active sites available for modification makes dendrimers ideal nanocarriers that can be modified to possess one or more targeting ligand attachments on each branch’s terminal site.
Application of Bioresponsive Polymers in Gene Delivery
Published in Deepa H. Patel, Bioresponsive Polymers, 2020
Tamgue Serges William, Drashti Pathak, Deepa H. Patel
They present very good characteristics: They are stable because of an efficient condensation of DNA;They have a small size (around 100 nm);They possess a high buffering capacity which allows them to cover a wide pH range, this capacity is called ‘proton sponge effect’ and it is due to important numbers of amino groups (primary, secondary, and tertiary) for branched polymers;They provide a good protection against nucleases degradation and a high efficient transfection capacity in vitro as well as in vivo possibly explained by the ‘sponge effect’ [7].
Small interfering RNA-based nanotherapeutics for treating skin-related diseases
Published in Expert Opinion on Drug Delivery, 2023
Yen-Tzu Chang, Tse-Hung Huang, Ahmed Alalaiwe, Erica Hwang, Jia-You Fang
Dendrimers are a novel generation of polymeric-based nanoparticles that promote the cutaneous absorption of small-molecular drugs and macromolecules. This polymer-based nanosystem exhibits a tree-like polymer structure to facilely modify the nanoparticle size. Dendrimers are comprised of three topological fragments: a focal core, building blocks with some interior layers having repeating units, and multiple peripheral functional groups. These branched polymers manifest special qualities of nanoscale diameter, multivalency, surface functionalization, and low polydispersity [59]. Dendrimers can interact with SC lipids to improve drug permeation. Charged dendrimers are reported to denature keratin in the SC layer to increase the transcellular diffusion of penetrants [60]. The high density of the cationic charge renders multiple attaching sites for siRNA molecules. The protection of RNA-based agents from nuclease is also a major concern in nucleic acid delivery. It has been proven that the complexation of siRNA molecules with dendrimers protects nucleic acids from enzymatic degradation [61]. The abundant tertiary amines in dendrimers promote the endosomal escape of siRNAs via a proton sponge effect [62]. It is expected that tertiary amines are protonated inside the endosomes. This effect disintegrates the endosome membrane, activating the release of cargos.
The development of peptide- and oligonucleotide-based drugs to prevent the formation of abnormal tau in tauopathies
Published in Expert Opinion on Drug Discovery, 2023
Madia Lozupone, Vittorio Dibello, Rodolfo Sardone, Fabio Castellana, Roberta Zupo, Luisa Lampignano, Ilaria Bortone, Roberta Stallone, Mario Altamura, Antonello Bellomo, Antonio Daniele, Vincenzo Solfrizzi, Francesco Panza
ASOs in general are unable to cross cellular membranes and blood-tissue barriers, such as the BBB, which is only permeable to lipophilic molecules of molecular weight<600 Da. Furthermore, ASOs must resist/escape intracellular degradation mechanisms, primarily with endogenous nucleases. There are three predominant strategies for the effective delivery of ASOs: (1) direct chemical alteration of the ASO molecule; (2) conjugation with specific targeting molecules, and (3) encapsulation in non-viral vesicles [123]. Within the CNS, increased efficiency in ASO delivery, protection from degradation, shielding the negative charge for more efficient cellular uptake, and lower immunogenicity can all be achieved through the encapsulation of ASOs in non-viral vectors including polymers. Also, polycationic dendrimers, which are highly branched polymers with easily modifiable surfaces, can be used as potential nonviral transfection nanocarriers [124].