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Acid degradable cationic galactose-based hyperbranched polymers as nano-therapeutic vehicles for Epidermal Growth Factor Receptor (EGFR) knockdown in Cervical Carcinoma.
In this study we synthetized by reversible addition-fragmentation chain transfer (RAFT) polymerization, several acid degradable galactose-based hyperbranched cationic polymers with varying molecular weights (10 to 20 kDa) and compositions with 2-lactobioamidoethyl methacrylamide [LAEMA] and 2- aminoethyl methacrylamide hydrochloride [AEMA] at different ratios (2.0, 1.0 & 0.5) and evaluated their ability to enhance Epidermal Growth Factor Receptor (EGFR) knockdown in cervical carcinoma. All the polymer constructs have enhanced capabilities to condensate siRNA (short interfering RNA), showing low toxicity at higher LAEMA...
Source: Biomacromolecules - August 29, 2018 Category: Biochemistry Authors: Peng YY, Diaz-Dussan D, Kumar P, Narain R Tags: Biomacromolecules Source Type: research

Cationic Hyperbranched Polymers with Biocompatible Shells for siRNA Delivery.
Abstract Cationic hyperbranched polymers (HBP) were prepared by self-condensing vinyl polymerization of an atom transfer radical polymerization (ATRP) inimer containing a quaternary ammonium group. Two types of biocompatible shells, poly(oligoethylene glycol) methacrylate (polyOEGMA) and poly(2-(methylsulfinyl) ethyl methacrylate) (polyDMSO), were grafted respectively from HBP core to form core-shell structures with low molecular weight dispersity and high biocompatibility, polyOEGMA-HBP and polyDMSO-HBP. Both of the structures showed low cytotoxicity and good siRNA complexing ability. The efficacy of gene silenci...
Source: Biomacromolecules - August 27, 2018 Category: Biochemistry Authors: Li S, Omi M, Cartieri F, Konkolewicz D, Mao G, Gao H, Averick SE, Mishina Y, Matyjaszewski K Tags: Biomacromolecules Source Type: research

Tunability of Biodegradable Poly(amine-co-ester) Polymers for Customized Nucleic Acid Delivery and Other Biomedical Applications.
Abstract Gene therapy promises to treat diseases that arise from genetic abnormalities by correcting the underlying cause of the disease rather than treating the associated symptoms. Successful transfer of nucleic acids into cells requires efficient delivery vehicles that protect the cargo and can penetrate the appropriate cellular barriers before releasing their contents. Many viral vectors and synthetic polycationic vectors for nucleic acid delivery do not translate well from in vitro to in vivo applications due to their instability and toxicity. We synthesized and characterized a library of biocompatible low ch...
Source: Biomacromolecules - August 15, 2018 Category: Biochemistry Authors: Kauffman AC, Piotrowski-Daspit AS, Nakazawa KH, Jiang Y, Datye A, Saltzman WM Tags: Biomacromolecules Source Type: research

Reversible Covalent-Crosslinked Polycations with Enhanced Stability and ATP-Responsive Behavior for Improved siRNA Delivery.
In this study, we proposed a new strategy of reversible-covalent crosslinking to enhance stability in circulation and enable stimuli-disassembly of polyplexes in tumor cells. Here, 25k polyethyleneimine (PEI) was chosen as model polycations for verifying the hypothesis. HA-PEI conjugation was formed by the crosslinking of adenosine triphosphate grafted HA (HA-ATP) with phenylboronic acid grafted PEI (PEI-PBA), via the chemical reaction between PBA and ATP. Compared with non-covalent polyplex by electrostatic interaction (HA/PEI), HA-PEI exhibited much better colloidal stability and serum stability. The covered HA-ATP layer...
Source: Biomacromolecules - August 6, 2018 Category: Biochemistry Authors: Zhou Z, Zhang M, Liu Y, Li C, Zhang Q, Oupicky D, Sun M Tags: Biomacromolecules Source Type: research

Correction to Fine Tuning of Core-Shell Structure of Hyaluronic Acid/Cell-Penetrating Peptides/siRNA Nanoparticles for Enhanced Gene Delivery to Macrophages in Antiatherosclerotic Therapy.
PMID: 30058804 [PubMed - as supplied by publisher]
Source: Biomacromolecules - July 30, 2018 Category: Biochemistry Authors: Zhao Y, He Z, Gao H, Tang H, He J, Guo Q, Zhang W, Liu J Tags: Biomacromolecules Source Type: research

Small Delivery Vehicles of siRNA for Enhanced Cancer Targeting.
Abstract Small interfering RNA (siRNA) drugs have been considered to treat various diseases in major organs. However, siRNA drugs developed for cancer therapy are hindered from proceeding to clinics. To date, various delivery formulations have been developed from cationic lipids, polymers, and/or inorganic nanoparticles for systemic siRNA delivery to solid tumors. Most of these delivery vehicles do not generate small particle sizes and pharmacokinetics required for accumulation in target cancer cells, compared with clinically tested anticancer drug-loaded polymeric micelles. This review describes the significance ...
Source: Biomacromolecules - June 4, 2018 Category: Biochemistry Authors: Kim HJ, Yi Y, Kim A, Miyata K 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

Tuned Density of Anti-Tissue Factor Antibody Fragment onto siRNA-loaded Polyion Complex Micelle for Optimizing Targetability into Pancreatic Cancer Cells.
Abstract Antibody fragment (Fab')-installed polyion complex (PIC) micelles were constructed to improve targetability of small interfering RNA (siRNA) delivery to pancreatic cancer cells. To this end, we synthesized a block copolymer of azide-functionalized poly(ethylene glycol) (PEG) and poly(L-lysine) (PLL), and prepared PIC micelles with siRNA. Then, a dibenzylcyclooctyne (DBCO)-modified anti-human tissue factor (TF) Fab' was conjugated to azido groups on the micellar surface. A fluorescence correlation spectroscopic (FCS) analysis revealed that 1, 2, or 3 molecule(s) of Fab'(s) were installed onto one micellar ...
Source: Biomacromolecules - May 16, 2018 Category: Biochemistry Authors: Min HS, Kim HJ, Ahn J, Naito M, Hayashi K, Toh K, Kim BS, Matsumura Y, Kwon IC, Miyata K, Kataoka K Tags: Biomacromolecules Source Type: research

Caged siRNAs with single cRGD modification for photo-regulation of exogenous and endogenous gene expression in cells and mice.
This study also suggested that photomodulation of target gene expression using single cRGD caged siRNA at 5' end of antisense strand RNA inhibited siRNA activity probably due to three factors: 1) trapping of cRGD modified siRNA in endosome and lysosome, 2) the steric hindrance of cRGD, 3) the binding of cRGD to its corresponding receptor. PMID: 29727579 [PubMed - as supplied by publisher]
Source: Biomacromolecules - May 4, 2018 Category: Biochemistry Authors: Yu L, Liang D, Chen C, Tang X Tags: Biomacromolecules Source Type: research

Co-Delivery of Doxorubicin and Anti-BCL-2 siRNA by pH-Responsive Polymeric Vector to Overcome Drug Resistance in In Vitro and In Vivo HepG2 Hepatoma Model.
In this study, triblock copolymer of poly(ethylene glycol)-block-poly(L-lysine)-block-poly aspartyl (N-(N',N'-diisopropylaminoethyl)) (PEG-PLL-PAsp(DIP)) was synthesized for the first time to enable the codelivery of BCL-2 siRNA and DOX. The system is supposed to only bypass drug efflux but also down-regulate the anti-apoptotic gene and consequently confronting against chemoresistance as well. Moreover, the pH responsive ability of the codelivery system can prevent drug leakage during circulation and guarantee swift release at tumors. The codelivered siRNA serves to suppress the expression of anti-apoptotic BCL-2 and conse...
Source: Biomacromolecules - April 24, 2018 Category: Biochemistry Authors: Sun W, Chen X, Xie C, Wang Y, Lin L, Zhu K, Shuai X Tags: Biomacromolecules Source Type: research

Fine tuning of core-shell structure of hyaluronic acid/cell-penetrating peptides/siRNA nanoparticles for enhanced gene delivery to macrophages in anti-atherosclerotic therapy.
Abstract Hyaluronic acid (HA)-coated LOX-1 specific siRNA-condensed cell-penetrating peptides (CPPs) nanocomplexes were developed for targeted gene delivery to macrophages and suppression of lipid accumulation. The HA coating facilitated the accumulation of nanoparticles at leaky endothelium overexpressing CD44 receptors and was further degraded by hyaluronidase (HAase) intra plaques for exposing the naked CPPs nanocomplexes (NCs) and achieving the ultimate location into macrophages. The surface coating of HA was verified by the increased particle size, inverted zeta potential, and TEM images. The targeting mechan...
Source: Biomacromolecules - April 11, 2018 Category: Biochemistry Authors: Zhao Y, He Z, Gao H, Tang H, He J, Guo Q, Zhang W, Liu J Tags: Biomacromolecules Source Type: research

Aqueous-soluble, acid-transforming chitosan for efficient and stimuli-responsive gene silencing.
This study demonstrates a molecularly engineered natural polymer for a biomedical application. PMID: 29562124 [PubMed - as supplied by publisher]
Source: Biomacromolecules - March 21, 2018 Category: Biochemistry Authors: Edson JA, Ingato D, Wu S, Lee B, Kwon YJ Tags: Biomacromolecules Source Type: research

Development of Fully Degradable Phosphonium-Functionalized Amphiphilic Diblock Copolymers for Nucleic Acids Delivery.
Abstract To expand the range of functional polymer materials to include fully hydrolytically degradable systems that bear bioinspired phosphorus-containing linkages both along the backbone and as cationic side chain moieties for packaging and delivery of nucleic acids, phosphonium-functionalized polyphosphoester- block-poly(l-lactide) copolymers of various compositions were synthesized, fully characterized, and their self-assembly into nanoparticles were studied. First, an alkyne-functionalized polyphosphoester- block-poly(l-lactide) copolymer was synthesized via a one pot sequential ring opening polymerization of...
Source: Biomacromolecules - March 11, 2018 Category: Biochemistry Authors: Borguet YP, Khan S, Noel A, Gunsten SP, Brody SL, Elsabahy M, Wooley KL Tags: Biomacromolecules Source Type: research

Cyclam-Modified PEI for Combined VEGF siRNA Silencing and CXCR4 Inhibition To Treat Metastatic Breast Cancer.
Abstract Chemokine receptor CXCR4 plays an important role in cancer cell invasion and metastasis. Recent findings suggest that anti-VEGF therapies upregulate CXCR4 expression, which contributes to resistance to antiangiogenic therapies. Here, we report the development of novel derivatives of polyethylenimine (PEI) that effectively inhibit CXCR4 while delivering anti-VEGF siRNA. PEI was alkylated with different amounts of a CXCR4-binding cyclam derivative to prepare PEI-C. Modification with the cyclam derivatives resulted in a considerable decrease in cytotoxicity when compared with unmodified PEI. All the PEI-C sh...
Source: Biomacromolecules - January 19, 2018 Category: Biochemistry Authors: Zhou Y, Yu F, Zhang F, Chen G, Wang K, Sun M, Li J, Oupický D Tags: Biomacromolecules Source Type: research

Highly Stable RNA Capture by Dense Cationic Polymer Brushes for the Design of Cytocompatible, Serum-Stable SiRNA Delivery Vectors.
Abstract The high density of polymer brushes confers to these coatings unique physico-chemical properties, in particular for the regulation of biomolecular interaction and the design of highly selective coatings for biosensors and protein patterning. Here we show that high density poly(dimethylaminoethyl methacrylate) cationic polymer brushes enable the stable uptake of high levels of oligonucleotides. This is proposed to result from the high degree of crowding and associated increase in entropic driving force for the binding of polyelectrolytes such as nucleic acid molecules. We further demonstrate the ease with ...
Source: Biomacromolecules - January 16, 2018 Category: Biochemistry Authors: Li D, Sharili AS, Connelly J, Gautrot JE Tags: Biomacromolecules Source Type: research

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