scholarly journals Endothelial siRNA delivery in nonhuman primates using ionizable low–molecular weight polymeric nanoparticles

2018 ◽  
Vol 4 (6) ◽  
pp. eaar8409 ◽  
Author(s):  
Omar F. Khan ◽  
Piotr S. Kowalski ◽  
Joshua C. Doloff ◽  
Jonathan K. Tsosie ◽  
Vasudevan Bakthavatchalu ◽  
...  
Keyword(s):  
Molecular Weight ◽  
Nonhuman Primates ◽  
Polymeric Nanoparticles ◽  
Sirna Delivery ◽  
Low Molecular Weight

scholarly journals In vivo endothelial siRNA delivery using polymeric nanoparticles with low molecular weight

2014 ◽  
Vol 9 (8) ◽  
pp. 648-655 ◽  
Author(s):  
James E. Dahlman ◽  
Carmen Barnes ◽  
Omar F. Khan ◽  
Aude Thiriot ◽  
Siddharth Jhunjunwala ◽  
...  
Keyword(s):  
Molecular Weight ◽  
Polymeric Nanoparticles ◽  
Sirna Delivery ◽  
Low Molecular Weight

scholarly journals Polymeric Nanoparticles Based on Tyrosine-Modified, Low Molecular Weight Polyethylenimines for siRNA Delivery

Pharmaceutics ◽  
2019 ◽  
Vol 11 (11) ◽  
pp. 600 ◽  
Author(s):  
Ewe ◽  
Noske ◽  
Karimov ◽  
Aigner
Keyword(s):  
Molecular Weight ◽  
Polymeric Nanoparticles ◽  
Sirna Delivery ◽  
Biological Properties ◽  
Low Molecular Weight ◽  
Rna Molecules ◽  
Low Cytotoxicity ◽  
Tyrosine Modification

A major hurdle for exploring RNA interference (RNAi) in a therapeutic setting is still the issue of in vivo delivery of small RNA molecules (siRNAs). The chemical modification of polyethylenimines (PEIs) offers a particularly attractive avenue towards the development of more efficient non-viral delivery systems. Here, we explore tyrosine-modified polyethylenimines with low or very low molecular weight (P2Y, P5Y, P10Y) for siRNA delivery. In comparison to their respective parent PEI, they reveal considerably increased knockdown efficacies and very low cytotoxicity upon tyrosine modification, as determined in different reporter and wildtype cell lines. The delivery of siRNAs targeting the anti-apoptotic oncogene survivin or the serine/threonine-protein kinase PLK1 (polo-like kinase 1; PLK-1) oncogene reveals strong inhibitory effects in vitro. In a therapeutic in vivo setting, profound anti-tumor effects in a prostate carcinoma xenograft mouse model are observed upon systemic application of complexes for survivin or PLK1 knockdown, in the absence of in vivo toxicity. We thus demonstrate the tyrosine-modification of (very) low molecular weight PEIs for generating efficient nanocarriers for siRNA delivery in vitro and in vivo, present data on their physicochemical and biological properties, and show their efficacy as siRNA therapeutic in vivo, in the absence of adverse effects.

scholarly journals Low-Molecular-Weight Polyethyleneimine Grafted Polythiophene for Efficient siRNA Delivery

2015 ◽  
Vol 2015 ◽  
pp. 1-9 ◽  
Author(s):  
Pan He ◽  
Kyoji Hagiwara ◽  
Hui Chong ◽  
Hsiao-hua Yu ◽  
Yoshihiro Ito
Keyword(s):  
Molecular Weight ◽  
Sirna Delivery ◽  
Fluorescent Microscopy ◽  
Molar Ratio ◽  
Low Molecular Weight ◽  
Label Free ◽  
Endosomal Membrane ◽  
Cationic Copolymers ◽  
Interfering Rna

Owing to its hydrophilicity, negative charge, small size, and labile degradation by endogenous nucleases, small interfering RNA (siRNA) delivery must be achieved by a carrier system. In this study, cationic copolymers composed of low-molecular-weight polyethylenimine and polythiophenes were synthesized and evaluated as novel self-tracking siRNA delivery vectors. The concept underlying the design of these copolymers is that hydrophobicity and rigidity of polythiophenes should enhance the transport of siRNA across the cell membrane and endosomal membrane. A gel retardation assay showed that the nanosized complexes formed between the copolymers and siRNA were stable even at a molar ratio of 1 : 2. The high cellular uptake (>80%) and localization of the copolymer vectors inside the cells were easily analyzed by tracking the fluorescence of polythiophene using fluorescent microscopy and cytometry. Anin vitroluciferase knockdown (KD) assay in A549-luc cells demonstrated that the siRNA complexes with more hydrophobic copolymers achieved a higher KD efficiency of 52.8% without notable cytotoxicity, indicating protein-specific KD activity rather than solely the cytotoxicity of the materials. Our polythiophene copolymers should serve as novel, efficient, low cell toxicity, and label-free siRNA delivery systems.

scholarly journals Polythiophenes with Cationic Phosphonium Groups as Vectors for Imaging, siRNA Delivery, and Photodynamic Therapy

Nanomaterials ◽  
2020 ◽  
Vol 10 (8) ◽  
pp. 1432
Author(s):  
Laure Lichon ◽  
Clément Kotras ◽  
Bauyrzhan Myrzakhmetov ◽  
Philippe Arnoux ◽  
Morgane Daurat ◽  
...  
Keyword(s):  
Molecular Weight ◽  
Photodynamic Therapy ◽  
Photophysical Properties ◽  
Combined Therapy ◽  
Sirna Delivery ◽  
Aqueous Media ◽  
Low Molecular Weight ◽  
Oxygen Species ◽  
Cationic Polymers ◽  
Intracellular Location

In this work, we exploit the versatile function of cationic phosphonium-conjugated polythiophenes to develop multifunctional platforms for imaging and combined therapy (siRNA delivery and photodynamic therapy). The photophysical properties (absorption, emission and light-induced generation of singlet oxygen) of these cationic polythiophenes were found to be sensitive to molecular weight. Upon light irradiation, low molecular weight cationic polythiophenes were able to light-sensitize surrounding oxygen into reactive oxygen species (ROS) while the highest were not due to its aggregation in aqueous media. These polymers are also fluorescent, allowing one to visualize their intracellular location through confocal microscopy. The most promising polymers were then used as vectors for siRNA delivery. Due to their cationic and amphipathic features, these polymers were found to effectively self-assemble with siRNA targeting the luciferase gene and deliver it in MDA-MB-231 cancer cells expressing luciferase, leading to 30–50% of the gene-silencing effect. In parallel, the photodynamic therapy (PDT) activity of these cationic polymers was restored after siRNA delivery, demonstrating their potential for combined PDT and gene therapy.

Low molecular weight chitosan–protamine conjugate for siRNA delivery with enhanced stability and transfection efficiency

RSC Advances ◽  
2016 ◽  
Vol 6 (112) ◽  
pp. 110951-110963 ◽  
Author(s):  
Sushilkumar Patil ◽  
Priyanka Bhatt ◽  
Rohan Lalani ◽  
Jitendra Amrutiya ◽  
Imran Vhora ◽  
...  
Keyword(s):  
Molecular Weight ◽  
Transfection Efficiency ◽  
Sirna Delivery ◽  
Low Molecular Weight ◽  
Low Molecular Weight Chitosan ◽  
Low Cytotoxicity ◽  
Enhanced Stability

Chitosan is among the few polymers with high biocompatibility and low cytotoxicity.

301 POSTER Use of low molecular weight polyethyleneimine conjugated to transferrin for siRNA delivery

2008 ◽  
Vol 6 (12) ◽  
pp. 97
Author(s):  
A. Grabowska ◽  
R. Kircheis ◽  
J. Kumari ◽  
P. Clarke ◽  
A. McKenzie ◽  
...  
Keyword(s):  
Molecular Weight ◽  
Sirna Delivery ◽  
Low Molecular Weight

Alkane-modified low-molecular-weight polyethylenimine with enhanced gene silencing for siRNA delivery

2013 ◽  
Vol 450 (1-2) ◽  
pp. 44-52 ◽  
Author(s):  
Gaoyang Guo ◽  
Li Zhou ◽  
Zhifei Chen ◽  
Weilin Chi ◽  
Xiuqun Yang ◽  
...  
Keyword(s):  
Molecular Weight ◽  
Gene Silencing ◽  
Sirna Delivery ◽  
Low Molecular Weight
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