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Source: Biomacromolecules

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Total 92 results found since Jan 2013.

Comparing gene silencing and physiochemical properties in siRNA bound cationic star-polymer complexes.
Abstract The translation of siRNA into clinical therapies has been significantly delayed by issues surrounding the delivery of naked siRNA to target cells. Here we investigate siRNA delivery by cationic acrylic polymers developed by Reversible Addition Fragmentation chain Transfer (RAFT) mediated free radical polymerization. We investigated cell uptake and gene silencing of a series of siRNA-star polymer complexes both in the presence and absence of a protein "corona". Using a multidisciplinary approach including quantitative nanoscale mechanical-atomic force microscopy, dynamic light scattering and nanoparticle t...
Source: Biomacromolecules - October 5, 2016 Category: Biochemistry Authors: Dearnley M, Reynolds NP, Cass P, Wei X, Shi S, Mohammed AA, Le T, Gunatillake P, Tizard ML, Thang SH, Hinton TM Tags: Biomacromolecules Source Type: research

Injectable, Guest-Host Assembled Polyethylenimine Hydrogel for siRNA Delivery.
Abstract While siRNA has tremendous potential for therapeutic applications, advancement is limited by poor delivery systems. Systemically, siRNAs are rapidly degraded, may have off-target silencing, and necessitate high working concentrations. To overcome this, we developed an injectable, guest-host assembled hydrogel between polyethylenimine (PEI) and polyethylene glycol (PEG) for local siRNA delivery. Guest-host modified polymers assembled with siRNAs to form polyplexes that had improved transfection and viability compared to PEI. At higher concentrations, these polymers assembled into shear-thinning hydrogels t...
Source: Biomacromolecules - December 19, 2016 Category: Biochemistry Authors: Wang LL, Sloand JN, Gaffey AC, Venkataraman CM, Wang Z, Trubelja A, Hammer DA, Atluri P, Burdick JA Tags: Biomacromolecules Source Type: research

Anionic polymer and quantum dot excipients to facilitate siRNA release and self-reporting of disassembly in stimuli-responsive nanocarrier formulations.
Abstract The incorporation of anionic excipients into polyplexes is a promising strategy for modulating siRNA binding vs. release and integrating diagnostic capabilities; however, specific design criteria and structure-function relationships are needed to facilitate the development of nanocarrier-based theranostics. Herein, we incorporated poly(acrylic acid) (PAA) and quantum dot (QD) excipients into photolabile siRNA polyplexes to increase gene silencing efficiencies by up to 100% and enable self-reporting of nanocarrier disassembly. Our systematic approach identified the functional relationships between gene sil...
Source: Biomacromolecules - April 25, 2017 Category: Biochemistry Authors: Greco CT, Andrechak JC, Epps Iii TH, Sullivan MO Tags: Biomacromolecules Source Type: research

Galactose Derivative-Modified Nanoparticles for Efficient siRNA Delivery to Hepatocellular Carcinoma.
In this study, we assembled lipid/calcium/phosphate nanoparticles (LCP NPs) conjugated with eight types of galactoside derivatives and demonstrated that phenyl β-d-galactoside-decorated LCP NPs (L4-LCP NPs) exhibited a superior siRNA delivery into HCC cells compared to normal hepatocytes. VEGF siRNAs delivered by L4-LCP NPs downregulated VEGF expression in HCC in vitro and in vivo and led to a potent antiangiogenic effect in the tumor microenvironment of a murine orthotopic HCC model. The efficient delivery of VEGF siRNA by L4-LCP NPs that resulted in significant tumor regression indicates that phenyl galactoside could be...
Source: Biomacromolecules - May 29, 2018 Category: Biochemistry Authors: Huang KW, Lai YT, Chern GJ, Huang SF, Tsai CL, Sung YC, Chiang CC, Hwang PB, Ho TL, Huang RL, Shiue TY, Chen Y, Wang SK Tags: Biomacromolecules Source Type: research

gH625 cell-penetrating peptide promotes the endosomal escape of nanovectorized siRNA in a triple negative breast cancer cell line.
Abstract The use of small interfering RNA (siRNA) to regulate oncogenes appears as a promising strategy in the context of cancer therapy, especially if they are vectorized by a smart delivery system. In the present study, we investigated the cellular trafficking of a siRNA nanovector (called CS-MSN) functionalized with the cell-penetrating peptides (CPP) gH625 in a triple negative breast cancer model. With complementary techniques, we showed that siRNA nanovectors were internalized by both clathrin- and caveolae-mediated endocytosis. The presence of gH625 at the surface of the siRNA nanovector did not modify the e...
Source: Biomacromolecules - July 14, 2019 Category: Biochemistry Authors: Ben Djemaa S, Herve-Aubert K, Lajoie L, Falanga A, Galdiero S, Nedellec S, Soucé M, Munnier E, Chourpa I, David S, Allard-Vannier E Tags: Biomacromolecules Source Type: research

Engineering the binding kinetics of synthetic polymer nanoparticles for siRNA delivery.
Abstract The affinity of a synthetic polymer nanoparticle (NP) to a target biomacromolecule is determined by the association and dissociation rate constants (kon, koff) of the interaction. The individual rates and their sensitivity to local environmental influences are important factors for the on demand capture and release a target biomacromolecule. Positively charged NPs for siRNA delivery is a case in point. The knockdown efficacy of siRNA can be strongly influenced by the binding kinetics to the NP. Here, we show that kon and koff of siRNA to NPs can be individually engineered by tuning the chemical structure ...
Source: Biomacromolecules - September 12, 2019 Category: Biochemistry Authors: Koide H, Fukuta T, Okishima A, Ariizumi S, Kiyokawa C, Tsuchida H, Nakamoto M, Yoshimatsu K, Ando H, Dewa T, Asai T, Oku N, Hoshino Y, Shea KJ Tags: Biomacromolecules Source Type: research

Polymer Nanocarrier System for Endosome Escape and Timed Release of siRNA with Complete Gene Silencing and Cell Death in Cancer Cells.
Abstract An influenza virus-inspired polymer mimic nanocarrier was used to deliver siRNA for specific and near complete gene knockdown of an osteoscarcom cell line (U-2SO). The polymer was synthesized by single-electron transfer living radical polymerization (SET-LRP) at room temperature to avoid complexities of transfer to monomer or polymer. It was the only LRP method that allowed good block copolymer formation with a narrow molecular weight distribution. At nitrogen to phosphorus (N/P) ratios of equal to or greater than 20 (greater than a polymer concentration of 13.8 μg/mL) with polo-like kinase 1 (PLK1) siRN...
Source: Biomacromolecules - September 4, 2013 Category: Biochemistry Authors: Gu W, Jia Z, Truong NP, Prasadam I, Xiao Y, Monteiro MJ Tags: Biomacromolecules Source Type: research

Highlighting the Role of Polymer Length, Carbohydrate Size, and Nucleic Acid Type in Potency of Glycopolycation Agents for pDNA and siRNA Delivery.
Abstract While nucleic acids such as small interfering RNA (siRNA) and plasmid DNA (pDNA) are promising research tools and therapeutic modalities, their potential in medical applications is limited by a fundamental mechanistic understanding and inadequate efficiency. Herein, two series of carbohydrate-based polycations were synthesized and examined that varied in the degree of polymerization (n)-one containing trehalose [Tr4(n) series: Tr4(23), Tr4(55), Tr4(77)] and the other containing beta-cyclodextrin [CD4(n) series: CD4(10), CD4(26), CD4(39), CD4(143), CD4(239)]. In addition, two monosaccharide models were exa...
Source: Biomacromolecules - September 13, 2013 Category: Biochemistry Authors: Xue L, Ingle NP, Reineke TM Tags: Biomacromolecules Source Type: research

The influence of oligospermine architecture on their suitability for siRNA delivery.
Abstract Spermines are naturally abundant polyamines, which partially condense nucleic acids and exhibit the "proton-sponge effect" in an acidic environment. However, spermine shows limited transfection efficiency of nucleic acids due to its low molecular weight. Therefore, spermines need to be modified to be used as non-viral vectors for nucleic acids. Here, we synthesized linear bisspermine, and linear and dendritic tetraspermine with different molecular architecture. These oligospermines have been self-assembled into polyplexes with siRNA. The structure-activity relationship of the oligospermines was evaluated ...
Source: Biomacromolecules - February 19, 2014 Category: Biochemistry Authors: Elsayed M, Corrand V, Kolhatkar V, Xie Y, Kim NH, Kolhatkar R, Merkel OM Tags: Biomacromolecules Source Type: research

Synthesis of Poly(meth)acrylates with Thioether and Tertiary Sulfonium Groups by ARGET ATRP and Their Use as siRNA Delivery Agents.
Abstract The field of RNA interference depends on the development of safe and efficient carriers for short interfering ribonucleic acid (siRNA) delivery. Conventional cationic monomers for siRNA delivery have utilized the nitrogen heteroatom to produce cationic charges. Here, we polymerized cationic sulfonium (meth)acrylate by activators regenerated by electron transfer (ARGET) atom transfer radical polymerization (ATRP) to form polymers with narrow molecular weight distributions for siRNA delivery. The tertiary sulfonium species was stable toward dealkylation in water but less stable in the polar aprotic solvent ...
Source: Biomacromolecules - December 17, 2014 Category: Biochemistry Authors: Mackenzie MC, Shrivats AR, Konkolewicz D, Averick SE, McDermott MC, Hollinger JO, Matyjaszewski K Tags: Biomacromolecules Source Type: research

Self-assembled Polypeptide Nanogels with Enzymatically Transformable Surface as an siRNA Delivery Platform.
Abstract Nanometer-size gel particles, or nanogels, have potential for delivering therapeutic macromolecules. A cationic surface promotes cellular internalization of nanogels but undesired electrostatic interactions, such as with blood components, cause instability and toxicities. Polyethylene glycol coating has been used to shield charges, but this decreases delivery efficiency. Technical difficulties in synthesis and controlling molecular weights make it unfeasible to, instead, coat with biodegradable polymers. Our proposed solution is cationized nanogels enzymatically functionalized with branched polysaccharide...
Source: Biomacromolecules - October 23, 2017 Category: Biochemistry Authors: Nishimura T, Yamada A, Umezaki K, Sawada SI, Mukai SA, Sasaki Y, Akiyoshi K Tags: Biomacromolecules Source Type: research

Insights into siRNA transfection in suspension: Efficient gene silencing in human mesenchymal stem cells encapsulated in hyaluronic acid hydrogel.
Abstract Small interfering RNAs (siRNAs) are powerful tools for post-transcriptional gene silencing which offers enormous opportunities for tissue engineering applications. However, poor serum stability, inefficient intracellular delivery, and inevitable toxicity of transfection reagents are the key barriers for their clinical translation. Thus innovative strategies that allow safe and efficient intracellular delivery of the nucleic acid drugs at the desired site is urgently needed for a smooth clinical translation of therapeutically appealing siRNA-based technology. In this regard, we have developed an innovative...
Source: Biomacromolecules - January 14, 2019 Category: Biochemistry Authors: Paidikondala M, Nawale GN, Varghese OP Tags: Biomacromolecules Source Type: research

Amphipathic Homopolymers for siRNA Delivery: Probing Impact of Bifunctional Polymer Composition on Transfection.
In this study, we systematically explore the influence of the lipophilic group on the siRNA transfection properties of the polycationic-based delivery vectors. For this, a novel and modular synthetic strategy was developed for the preparation of polymers carrying a cationic site and a lipophilic group at each polymer repeat unit. These bifunctional polymers could form a complex with siRNA and deliver it to human colon carcinoma cells (HT-29-luc). In general, transfection capability increased with an increase in the chain length of the lipophilic moiety. The best transfection agent, a polymer containing ammonium groups and ...
Source: Biomacromolecules - April 22, 2014 Category: Biochemistry Authors: Buerkli C, Lee SH, Moroz E, Stuparu MC, Leroux JC, Khan A Tags: Biomacromolecules Source Type: research

Dual MMP7-Proximity-Activated and Folate Receptor-Targeted Nanoparticles for siRNA Delivery.
Abstract A dual-targeted siRNA nanocarrier has been synthesized and validated that is selectively activated in environments where there is colocalization of two breast cancer hallmarks, elevated matrix metalloproteinase (MMP) activity and folate receptor overexpression. This siRNA nanocarrier is self-assembled from two polymers containing the same pH-responsive, endosomolytic core-forming block but varying hydrophilic, corona-forming blocks. The corona block of one polymer consists of a 2 kDa PEG attached to a distal folic acid (FA); the second polymer contains a larger (Y-shaped, 20 kDa) PEG attached to the core ...
Source: Biomacromolecules - November 21, 2014 Category: Biochemistry Authors: Li H, Miteva M, Kirkbride KC, Cheng MJ, Nelson CE, Simpson EM, Gupta MK, Duvall CL, Giorgio TD Tags: Biomacromolecules Source Type: research

Enzyme- and pH-responsive microencapsulated nanogels for oral delivery of siRNA to induce TNF-α knockdown in the intestine.
Abstract Inflammatory bowel diseases (IBD) manifest from excessive intestinal inflammation. Local delivery of siRNA that targets these inflammatory cytokines would provide a novel treatment approach. Microencapsulated nanogels are designed and validated as platforms for oral delivery of siRNA targeting TNF-α, a common clinical target of IBD treatments. The preferred platform was designed to (i) protect siRNA-loaded nanogels from the harsh acidic environment of the upper GI tract; and (ii) enzymatically degrade and release the nanogels once the carrier has reached the intestinal region. This platform consists of m...
Source: Biomacromolecules - January 26, 2016 Category: Biochemistry Authors: Knipe JM, Strong LE, Peppas NA Tags: Biomacromolecules Source Type: research