Thiourea-Functional Bioreducible Poly(amido amine)s in Gene Delivery

Elzes, M. Rachèl; Si, Guoying; Engbersen, Johan F.J.

doi:10.1021/bk-2019-1309.ch005

Cited by 4 publications

(5 citation statements)

References 180 publications

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“…The three-dimensional structures of the selected molecules were built in Maestro molecular modelling environment (Maestro release 2018) and minimized using MacroModel software (MacroModel, Schrödinger, LLC, New York, NY, 2018) as previously described [28] , [29] . Furthermore, LigPrep (LigPrep, Schrödinger, LLC, New York, NY, 2018) application was used to refine the chemical structures.…”

Section: Methodsmentioning

confidence: 99%

“…Among the selected compounds, 3-pyridyl-isothiocyanate ( 25 ) showed the highest H 2 S releasing ability. This compound has been employed in a different research field as starting material for the synthesis of cationic polymers for targeted delivery [27] , [28] . Here we describe it as an efficient H 2 S donor that was thoroughly studied for its pharmacological activity in different experimental models of I/R injury in rats.…”

Section: Introductionmentioning

confidence: 99%

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Structure-activity relationships study of isothiocyanates for H2S releasing properties: 3-Pyridyl-isothiocyanate as a new promising cardioprotective agent

Citi

Corvino

Fiorino

et al. 2021

Journal of Advanced Research

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Section: Methodsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Structure-activity relationships study of isothiocyanates for H2S releasing properties: 3-Pyridyl-isothiocyanate as a new promising cardioprotective agent

Citi

Corvino

Fiorino

et al. 2021

Journal of Advanced Research

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“…Polymer hydroxylation 40 or PEGylation 41 may be employed to decrease protein binding, but it can also lead to less efficient DNA packing and lowered transfection efficiencies. 42 Strengthening polymer−DNA interactions by incorporating additional stabilizing forces such as aromatic intercalation, 43 hydrogen bonds, 44 physical crosslinks, 45 and chemical cross-links 46 reduces the nonspecific binding of serum proteins and the resulting aggregation, yet these additional interactions may also hinder transfection. 42 The introduction of hydrophobic moieties helps shield the polyplexes from the adherence of anionic blood components and prevents dissociation by serum proteins.…”

Section: ■ Introductionmentioning

confidence: 99%

Linear Poly(ethylenimine-propylenimine) Random Copolymers for Gene Delivery: From Polymer Synthesis to Efficient Transfection with High Serum Tolerance

et al. 2022

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Naturally occurring oligoamines, such as spermine, spermidine, and putrescine, are well-known regulators of gene expression. These oligoamines frequently have short alkyl spacers with varying lengths between the amines. Linear polyethylenimine (PEI) is a polyamine that has been widely applied as a gene vector, with various formulations currently in clinical trials. In order to emulate natural oligoamine gene regulators, linear random copolymers containing both PEI and polypropylenimine (PPI) repeat units were designed as novel gene delivery agents. In general, statistical copolymerization of 2-oxazolines and 2-oxazines leads to the formation of gradient copolymers. In this study, however, we describe for the first time the synthesis of near-ideal random 2-oxazoline/2-oxazine copolymers through careful tuning of the monomer structures and reactivity as well as polymerization conditions. These copolymers were then transformed into near-random PEI–PPI copolymers by controlled side-chain hydrolysis. The prepared PEI–PPI copolymers formed stable polyplexes with GFP-encoding plasmid DNA, as validated by dynamic light scattering. Furthermore, the cytotoxicity and transfection efficiency of polyplexes were evaluated in C2C12 mouse myoblasts. While the polymer chain length did not significantly increase the toxicity, a higher PPI content was associated with increased toxicity and also lowered the amount of polymers needed to achieve efficient transfection. The transfection efficiency was significantly influenced by the degree of polymerization of PEI–PPI, whereby longer polymers resulted in more transfected cells. Copolymers with 60% or lower PPI content exhibited a good balance between high plasmid–DNA transfection efficiency and low toxicity. Interestingly, these novel PEI–PPI copolymers revealed exceptional serum tolerance, whereby transfection efficiencies of up to 53% of transfected cells were achieved even under 50% serum conditions. These copolymers, especially PEI–PPI with DP500 and a 1:1 PEI/PPI ratio, were identified as promising transfection agents for plasmid DNA.

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“…Cationic polymers have commonly been used to form polyplexes with DNA − and proteins − to achieve cytosolic delivery. Poly(amido amine)s have been widely used in gene delivery. , These peptidomimetic polymers contain amines, which can be protonated intracellularly through the proton sponge effect and present the ease of integrating disulfide moieties for biodegradability. ,, pCBA-ABOL, a copolymer containing N , N -bis(acryloyl) cystamine and 4-amino-1-butanol, is degradable in the presence of glutathione and has shown promising gene transfection results …”

Section: Introductionmentioning

confidence: 99%

“…36,37 These peptidomimetic polymers contain amines, which can be protonated intracellularly through the proton sponge effect and present the ease of integrating disulfide moieties for biodegradability. 30,37,38 pCBA-ABOL, a copolymer containing N,N-bis(acryloyl) cystamine and 4-amino-1-butanol, is degradable in the presence of glutathione and has shown promising gene transfection results. 30 Here, we explore the use of a cationic, reducible polymerbased vector to traffic anionically charged SCNPs to the cytosol.…”

Section: ■ Introductionmentioning

confidence: 99%

Enhancing Cellular Internalization of Single-Chain Polymer Nanoparticles via Polyplex Formation

2022

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Intracellular delivery of nanoparticles is crucial in nanomedicine to reach optimal delivery of therapeutics and imaging agents. Single-chain polymer nanoparticles (SCNPs) are an interesting class of nanoparticles due to their unique site range of 5−20 nm. The intracellular delivery of SCNPs can be enhanced by using delivery agents. Here, a positive polymer is used to form polyplexes with SCNPs, similar to the strategy of protein and gene delivery. The size and surface charge of the polyplexes were evaluated. The cellular uptake showed rapid uptake of SCNPs via polyplex formation, and the cytosolic delivery of the SCNPs was presented by confocal microscopy. The ability of SCNPs to act as nanocarriers was further explored by conjugation of doxorubicin.

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Thiourea-Functional Bioreducible Poly(amido amine)s in Gene Delivery

Cited by 4 publications

References 180 publications

Structure-activity relationships study of isothiocyanates for H2S releasing properties: 3-Pyridyl-isothiocyanate as a new promising cardioprotective agent

Structure-activity relationships study of isothiocyanates for H2S releasing properties: 3-Pyridyl-isothiocyanate as a new promising cardioprotective agent

Linear Poly(ethylenimine-propylenimine) Random Copolymers for Gene Delivery: From Polymer Synthesis to Efficient Transfection with High Serum Tolerance

Enhancing Cellular Internalization of Single-Chain Polymer Nanoparticles via Polyplex Formation

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