<i>In silico</i> study of PEI-PEG-squalene-dsDNA polyplex formation: the delicate role of the PEG length in the binding of PEI to DNA

Vasiliu, Tudor; Craciun, Bogdan Florin; Neamţu, Andrei; Clima, Lilia; Isac, Dragoş Lucian; Maier, Stelian Sergiu; Pinteala, Mariana; Mocci, Francesca; Laaksonen, Aatto

doi:10.1039/d1bm00973g

Cited by 9 publications

(8 citation statements)

References 64 publications

(63 reference statements)

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Section: Introductionmentioning

confidence: 99%

“…[3] Among them, hyperbranched polymers, especially hyperbranched polyethyleneimines (PEIs), show higher solubility and lower viscosity than corresponding linear polymers, which is beneficial for their applications. [4,5] PEIs and their derivatives possess highly branched peripherals containing plenty of amino groups, which makes them widely used as polyprotic bases and polydentate ligands. [6,7] In addition, their active amino groups provide convenient ways for further modification to develop new derivatives.…”

Section: Introductionmentioning

confidence: 99%

“…[24] Furthermore, modification with long polymer chains also tends to weaken the inherent properties from PEIs. [25] Thermoresponsive PEIs with amide end groups were also prepared, but they exhibit a relative broad phase transitions. [26,27] In our previous work, we found that introduction of oligoethylene glycol (OEG)-based dendrons to the side chain of linear polymers (polymethacrylate, polyphenylacetylene, and polypeptide) can afford them unprecedented thermoresponsiveness.…”

Section: Introductionmentioning

confidence: 99%

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Dendronized Hyperbranched Polyethyleneimines with Switchable Thermoresponsiveness and Encapsulation

Yao,

Liu,

Song

et al. 2023

Macro Chemistry & Physics

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Hyperbranched polyethyleneimines (PEIs) with multiple layered structures and high density of terminal amino groups have shown great potentials for applications in biomedicine, sensors, and catalysis. In this work, a kind of dendronized hyperbranched PEIs (DHPs) was synthesized by modification of PEIs with dendritic oligoethylene glycols (OEGs). These DHPs not only inherit the characteristic thermoresponsive behavior from the OEG dendrons, but also show low cytotoxicity and switchable encapsulation capacities. Their thermoresponsive behavior was found to be mainly dependent on the coverage and amphiphilicity of dendritic OEGs, solution pH, and NaCl concentration. Moreover, DHPs exhibit advantages in thermally‐switchable complexation with guest molecules because of their adjustable crowding effect from the densely packed OEG chains. In addition, these DHPs can also be used as nanoreactors, which can reduce metal ions into metal nanoparticles in a convenient way. In virtue of these peculiarities, we believe these dendronized hyperbranched PEIs with smart properties can be used as promising scaffolds in drug‐controlled release and nanoreactors.This article is protected by copyright. All rights reserved

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Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Dendronized Hyperbranched Polyethyleneimines with Switchable Thermoresponsiveness and Encapsulation

Yao,

Liu,

Song

et al. 2023

Macro Chemistry & Physics

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“…As another gold standard in non-viral gene delivery, high molecular weight (HMW) PEI also faces the quandary of being highly efficient in transfection and toxic at the same time [17][18][19]. Fortunately, PEI possesses abundant reactive amine groups for versatile functionalization and has the potential to be decorated as a stand-alone DNA condensing agent [20][21][22][23]. Interestingly, it has also been found that PEI can promote the nuclear entry of DNA for transcription while lipid-bound DNA is not transcription-active [24,25].…”

Section: Introductionmentioning

confidence: 99%

Chitosan-Crosslinked Low Molecular Weight PEI-Conjugated Iron Oxide Nanoparticle for Safe and Effective DNA Delivery to Breast Cancer Cells

et al. 2022

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Breast cancer has attracted tremendous research interest in treatment development as one of the major threats to public health. The use of non-viral carriers for therapeutic DNA delivery has shown promise in treating various cancer types, including breast cancer, due to their high DNA loading capacity, high cell transfection efficiency, and design versatility. However, cytotoxicity and large sizes of non-viral DNA carriers often raise safety concerns and hinder their applications in the clinic. Here we report the development of a novel nanoparticle formulation (termed NP-Chi-xPEI) that can safely and effectively deliver DNA into breast cancer cells for successful transfection. The nanoparticle is composed of an iron oxide core coated with low molecular weight (800 Da) polyethyleneimine crosslinked with chitosan via biodegradable disulfide bonds. The NP-Chi-xPEI can condense DNA into a small nanoparticle with the overall size of less than 100 nm and offer full DNA protection. Its biodegradable coating of small-molecular weight xPEI and mildly positive surface charge confer extra biocompatibility. NP-Chi-xPEI-mediated DNA delivery was shown to achieve high transfection efficiency across multiple breast cancer cell lines with significantly lower cytotoxicity as compared to the commercial transfection agent Lipofectamine 3000. With demonstrated favorable physicochemical properties and functionality, NP-Chi-xPEI may serve as a reliable vehicle to deliver DNA to breast cancer cells.

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“…Multivalent counterions are present also in viruses, neutralizing the negatively-charged DNA and RNA macromolecules, and allowing them to pack densely inside the small volume of the viral capsid (Ames and Dubin, 1960;Roos et al, 2007;Carrivain et al, 2012;Mounce et al, 2017;Firpo and Mounce, 2020). The interactions of positively-charged PAs with DNA have a significant biological effect, and are also involved in some emerging biotechnological applications (Korolev et al, 2001;D'Agostino, 2018;Perepelytsya et al, 2019;Mocci et al, 2021;Vasiliu et al, 2021). The study of the role of PAs in the structural organization of DNA in living organisms is of paramount importance for the understanding of key biological functions.…”

Section: Introductionmentioning

confidence: 99%

Caging Polycations: Effect of Increasing Confinement on the Modes of Interaction of Spermidine3+ With DNA Double Helices

Vasiliu¹,

Mocci

Laaksonen

et al. 2022

Front. Chem.

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Polyamines have important roles in the modulation of the cellular function and are ubiquitous in cells. The polyamines putrescine2+, spermidine3+, and spermine4+ represent the most abundant organic counterions of the negatively charged DNA in the cellular nucleus. These polyamines are known to stabilize the DNA structure and, depending on their concentration and additional salt composition, to induce DNA aggregation, which is often referred to as condensation. However, the modes of interactions of these elongated polycations with DNA and how they promote condensation are still not clear. In the present work, atomistic molecular dynamics (MD) computer simulations of two DNA fragments surrounded by spermidine3+ (Spd3+) cations were performed to study the structuring of Spd3+ “caged” between DNA molecules. Microsecond time scale simulations, in which the parallel DNA fragments were constrained at three different separations, but allowed to rotate axially and move naturally, provided information on the conformations and relative orientations of surrounding Spm3+ cations as a function of DNA-DNA separation. Novel geometric criteria allowed for the classification of DNA-Spd3+ interaction modes, with special attention given to Spd3+ conformational changes in the space between the two DNA molecules (caged Spd3+). This work shows how changes in the accessible space, or confinement, around DNA affect DNA-Spd3+ interactions, information fundamental to understanding the interactions between DNA and its counterions in environments where DNA is compacted, e.g. in the cellular nucleus.

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In silico study of PEI-PEG-squalene-dsDNA polyplex formation: the delicate role of the PEG length in the binding of PEI to DNA

Abstract: The biocompatible hydrophilic polyethylene glycol (PEG) is widely used in biomedical applications, such as drug or gene delivery, tissue engineering or as antifouling in biomedical devices. Experimental studies have shown...

Cited by 9 publications

References 64 publications

Dendronized Hyperbranched Polyethyleneimines with Switchable Thermoresponsiveness and Encapsulation

Dendronized Hyperbranched Polyethyleneimines with Switchable Thermoresponsiveness and Encapsulation

Chitosan-Crosslinked Low Molecular Weight PEI-Conjugated Iron Oxide Nanoparticle for Safe and Effective DNA Delivery to Breast Cancer Cells

Caging Polycations: Effect of Increasing Confinement on the Modes of Interaction of Spermidine3+ With DNA Double Helices

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