Dataset Information

Enhancing Gene-Knockdown Efficiency of Poly(N-isopropylacrylamide) Nanogels.

ABSTRACT: Polo-like-kinase 1 (PLK1), which is a serine-threonine protein kinase overexpressed in cancer cells, is known to regulate tumor growth and have recently gathered attention as a target gene for RNA interference because of the poor bioavailability and nonspecificity of the available inhibitors. However, the lower transfection efficiency of siRNA and its poor stability in biological mileu necessitate the need of efficient siRNA delivery systems. Here, we report efficacious polymeric nanoparticles for the delivery of PLK1 siRNA in mammalian cancer cells. N-Isopropylacrylamide (NIPAm) and N-isopropylmethacrylamide-co-NIPAm nanogels were synthesized and modified using poly-ε-lysine. Furthermore, their ability to induce gene silencing was investigated by flow cytometry and real-time polymerase chain reaction, and the silencing efficiency observed was related to the polymer composition and its effect on the gene loading and protection ability and the endosomal escape capability. This study attempts to leverage the understanding of the cell-material interaction, thus, addressing the bottlenecks of siRNA delivery for enhancing the efficacy of the poly(N-isopropylacrylamide)-based delivery vehicle.

SUBMITTER: Deshpande S

PROVIDER: S-EPMC6072245 | biostudies-literature | 2018 Jul

REPOSITORIES: biostudies-literature

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Enhancing Gene-Knockdown Efficiency of Poly(<i>N</i>-isopropylacrylamide) Nanogels.

Deshpande Sonal S Patil Smita S Singh Neetu N

ACS omega 20180718 7

Polo-like-kinase 1 (PLK1), which is a serine-threonine protein kinase overexpressed in cancer cells, is known to regulate tumor growth and have recently gathered attention as a target gene for RNA interference because of the poor bioavailability and nonspecificity of the available inhibitors. However, the lower transfection efficiency of siRNA and its poor stability in biological mileu necessitate the need of efficient siRNA delivery systems. Here, we report efficacious polymeric nanoparticles f ...[more]

PMID: 30087933

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Project description:This work represents a detailed investigation into the phase and morphological behavior of synergistic dual-stimuli-responsive poly(N-isopropylacrylamide) nanogels, a material that is of considerable interest as a matrix for in situ forming implants. Nanogels were synthesized with four different diameters (65, 160, 310, and 450 nm) as monodispersed particles. These different samples were then prepared and characterized as both dilute (0.1 wt %) and concentrated dispersions (2-22 wt %). In the dilute form, all of the nanogels had the same response to the triggers of the physiological temperature and ionic strength. In water, the nanogels would deswell when heated above 32 °C, while they would aggregate if heated above this temperature at the physiological ionic strength. In the concentrated form, the nanogels exhibited a wide range of morphological changes, with liquid, swollen gel, shrunken gel, and aggregate structures all possible. The occurrence of these structures was dependent on many factors such as the temperature, ionic strength of the solvent, size and ζ-potential of the nanogel, and dispersion concentration. We explored these factors in detail with techniques such as visual studies, rheology, effective volume fraction, and shape factor measurement. The different-sized nanogels displayed differing phase and morphological behavior, but generally higher concentrations of the nanogels (>7 wt %) yielded gels in water with the transitions depending on the temperature. The smallest nanogel (65 nm diameter) exhibited the most unique behavior; it did not form a swollen gel at any concentration tested. Shape factor measurement for the nanogel samples showed that two of the larger three samples (160 and 310 nm) had core-shell structures with denser core cross-linking, while the smallest nanogel sample displayed a homogeneous cross-linked structure. We hypothesize that the smallest nanogels are able to undergo more extensive interpenetration compared to the larger nanogels, which meant that the smallest nanogel was not able to form a swollen gel. In the presence of salt at 12 wt %, all of the nanogels formed aggregates when heated above 35 °C due to the screening of the electrostatic stabilization by the salt. This work revealed unique behavior of the smallest nanogel with a homogeneous cross-linked structure; its phase and morphological behavior were unlike a particle dispersion, rather these were more similar to those of a branched polymer solution. In total, these findings can be used to provide information about the design of poly(N-isopropylacrylamide) nanogel dispersions for different applications where highly specific spatiotemporal control of morphology is required, for example, in the formation of in situ forming implants or for pore blocking behavior.

Dataset Information

Enhancing Gene-Knockdown Efficiency of Poly(N-isopropylacrylamide) Nanogels.

Publications

Enhancing Gene-Knockdown Efficiency of Poly(<i>N</i>-isopropylacrylamide) Nanogels.

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