scholarly journals Amphiphilic Polypeptides for VEGF siRNA Delivery into Retinal Epithelial Cells

Pharmaceutics ◽  
2020 ◽  
Vol 12 (1) ◽  
pp. 39 ◽  
Author(s):  
Olga Osipova ◽  
Vladimir Sharoyko ◽  
Natalia Zashikhina ◽  
Natalya Zakharova ◽  
Tatiana Tennikova ◽  
...  
Keyword(s):  
Drug Release ◽  
Self Assembly ◽  
Messenger Rna ◽  
Sirna Delivery ◽  
Aqueous Media ◽  
Size Exclusion ◽  
Nucleic Acid Delivery ◽  
Cationic Polymers ◽  
Polymer Carriers ◽  
Exclusion Chromatography

Polyethyleneimine, poly-L-lysine, chitosan and some others cationic polymers have been thoroughly studied as nucleic acid delivery systems in gene therapy. However, the drug release from these systems proceeds at a very low rate due to extremely high binding between a carrier and gene material. To reduce these interactions and to enhance drug release, we developed a set of amphiphilic polypeptides containing positively and negatively charged amino acids as well as a hydrophobic one. The copolymers obtained were characterized by size-exclusion chromatography, static light scattering, HPLC amino acid analysis and 1HNMR spectroscopy. All copolymers formed particles due to a self-assembly in aqueous media. Depending on polypeptide composition, the formation of particles with hydrodynamic diameters from 180 to 900 nm was observed. Stability of polymer particles, loading and release efficiency were carefully studied. Cellular uptake of the particles was efficient and their cytotoxicity was negligible. The application of polymer carriers, containing siRNA, to vascular endothelial growth factor (VEGF-A165) silencing of ARPE-19 cells was successful. The gene silencing was confirmed by suppression of both messenger RNA and protein expression.

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.

Aqueous size-exclusion chromatography of cationic polymers for gene delivery

2006 ◽  
Vol 116 (2) ◽  
pp. e69-e71
Author(s):  
X. Jiang ◽  
A. van der Horst ◽  
M.J. van Steenbergen ◽  
N. Akeroyd ◽  
C.F. van Nostrum ◽  
...  
Keyword(s):  
Gene Delivery ◽  
Size Exclusion Chromatography ◽  
Size Exclusion ◽  
Cationic Polymers ◽  
Exclusion Chromatography

scholarly journals mRNA and miRNA Profiles of Exosomes from Cultured Tumor Cells Reveal Biomarkers Specific for HPV16-Positive and HPV16-Negative Head and Neck Cancer

2020 ◽  
Vol 21 (22) ◽  
pp. 8570
Author(s):  
Sonja Ludwig ◽  
Priyanka Sharma ◽  
Petra Wise ◽  
Richard Sposto ◽  
Deborah Hollingshead ◽  
...  
Keyword(s):  
Head And Neck Cancer ◽  
Head And Neck ◽  
Neck Cancer ◽  
Messenger Rna ◽  
Expression Profiles ◽  
Size Exclusion ◽  
Host Immune System ◽  
Cell Lysates ◽  
Hpv Status ◽  
Exclusion Chromatography

Human papillomavirus (HPV)(+) and HPV(−) head and neck cancer (HNC) cells’ interactions with the host immune system are poorly understood. Recently, we identified molecular and functional differences in exosomes produced by HPV(+) vs. HPV(−) cells, suggesting that genetic cargos of exosomes might identify novel biomarkers in HPV-related HNCs. Exosomes were isolated by size exclusion chromatography from supernatants of three HPV(+) and two HPV(−) HNC cell lines. Paired cell lysates and exosomes were analyzed for messenger RNA (mRNA) by qRT-PCR and microRNA (miR) contents by nanostring analysis. The mRNA profiles of HPV(+) vs. HPV(−) cells were distinct, with EGFR, TP53 and HSPA1A/B overexpressed in HPV(+) cells and IL6, FAS and DPP4 in HPV(−) cells. The mRNA profiles of HPV(+) or HPV(−) exosomes resembled the cargo of their parent cells. miR expression profiles in cell lysates identified 8 miRs expressed in HPV(−) cells vs. 14 miRs in HPV(+) cells. miR-205-5p was exclusively expressed in HPV(+) exosomes, and miR-1972 was only detected in HPV(−) exosomes. We showed that HPV(+) and HPV(−) exosomes recapitulated the mRNA expression profiles of their parent cells. Expression of miRs was dependent on the HPV status, and miR-205-5p in HPV(+) and miR-1972 in HPV(−) exosomes emerge as potential discriminating HPV-associated biomarkers.

scholarly journals Tyrosine-Modification of Polypropylenimine (PPI) and Polyethylenimine (PEI) Strongly Improves Efficacy of siRNA-Mediated Gene Knockdown

Nanomaterials ◽  
2020 ◽  
Vol 10 (9) ◽  
pp. 1809 ◽  
Author(s):  
Sandra Noske ◽  
Michael Karimov ◽  
Achim Aigner ◽  
Alexander Ewe
Keyword(s):  
Sirna Delivery ◽  
Nucleic Acid Delivery ◽  
Cationic Polymers ◽  
Small Interfering Rnas ◽  
Polymeric Systems ◽  
Rna Molecules ◽  
First Time ◽  
Tyrosine Modification

The delivery of small interfering RNAs (siRNA) is an efficient method for gene silencing through the induction of RNA interference (RNAi). It critically relies, however, on efficient vehicles for siRNA formulation, for transfection in vitro as well as for their potential use in vivo. While polyethylenimines (PEIs) are among the most studied cationic polymers for nucleic acid delivery including small RNA molecules, polypropylenimines (PPIs) have been explored to a lesser extent. Previous studies have shown the benefit of the modification of small PEIs by tyrosine grafting which are featured in this paper. Additionally, we have now extended this approach towards PPIs, presenting tyrosine-modified PPIs (named PPI-Y) for the first time. In this study, we describe the marked improvement of PPI upon its tyrosine modification, leading to enhanced siRNA complexation, complex stability, siRNA delivery, knockdown efficacy and biocompatibility. Results of PPI-Y/siRNA complexes are also compared with data based on tyrosine-modified linear or branched PEIs (LPxY or PxY). Taken together, this establishes tyrosine-modified PPIs or PEIs as particularly promising polymeric systems for siRNA formulation and delivery.

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