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Source: Biomaterials

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Total 156 results found since Jan 2013.

Multifunctional, self-assembling anionic peptide-lipid nanocomplexes for targeted siRNA delivery.
Abstract Formulations of cationic liposomes and polymers readily self-assemble by electrostatic interactions with siRNA to form cationic nanoparticles which achieve efficient transfection and silencing in vitro. However, the utility of cationic formulations in vivo is limited due to rapid clearance from the circulation, due to their association with serum proteins, as well as systemic and cellular toxicity. These problems may be overcome with anionic formulations but they provide challenges of self-assembly and transfection efficiency. We have developed anionic, siRNA nanocomplexes utilizing anionic PEGylated li...
Source: Biomaterials - June 28, 2014 Category: Materials Science Authors: Tagalakis AD, Lee DH, Bienemann AS, Zhou H, Munye MM, Saraiva L, McCarthy D, Du Z, Vink CA, Maeshima R, White EA, Gustafsson K, Hart SL Tags: Biomaterials Source Type: research

Co-delivery of Cbfa-1-targeting siRNA and SOX9 protein using PLGA nanoparticles to induce chondrogenesis of human mesenchymal stem cells.
This study evaluated the abilities of SOX9, a crucial protein during the early stage of chondrogenesis, and siRNA targeting Cbfa-1, a transcription factor that promotes osteogenesis, to stimulate chondrogenesis. Non-toxic poly-(d,l-lactide-co-glycolide) (PLGA) nanoparticles (NPs) were coated with Cbfa-1-targeting siRNA and loaded with SOX9 protein. Coomassie blue staining and circular dichroism revealed that the loaded SOX9 protein maintained its stability and bioactivity. These NPs easily entered human mesenchymal stem cells (hMSCs) in vitro and caused them to differentiate into chondrocytes. Markers that are typically e...
Source: Biomaterials - June 23, 2014 Category: Materials Science Authors: Jeon SY, Park JS, Yang HN, Lim HJ, Yi SW, Park H, Park KH Tags: Biomaterials Source Type: research

Targetable micelleplex hydrogel for long-term, effective, and systemic siRNA delivery.
Abstract We developed a targetable micelleplex hydrogel as a new efficient systemic siRNA delivery material that functions as a targetable gene carrier, and a hydrogel capable of controlled release to overcome drawbacks of multiple administrations of systemic siRNA carriers due to decreased fluctuation of them in the serum. The micelleplexes, complexes between polymeric micelles and siRNAs could turn into gel after subcutaneous injection and be slowly released from the gel. The released micelleplexes selectively accumulated in the tumor and showed anti-tumor effect due to gene silencing for an extended period of t...
Source: Biomaterials - June 17, 2014 Category: Materials Science Authors: Kim YM, Song SC Tags: Biomaterials Source Type: research

PEGylated carboxymethyl chitosan/calcium phosphate hybrid anionic nanoparticles mediated hTERT siRNA delivery for anticancer therapy.
In this study, we synthesized a pH-sensitive polymer of PEG grafted carboxymethyl chitosan (PEG-CMCS) and developed anionic-charged hybrid nanoparticles of PEG-CMCS and calcium phosphate (CaP) for siRNA delivery through a single-step self-assembly method in aqueous condition. The formed nanoparticles with charge of around -8.25 mv and average diameter of 102.1 nm exhibited efficient siRNA encapsulation and enhanced colloidal and serum stability. The test in vitro indicated that the nanoparticles entered into HepG2 cells by endocytosis, and achieved endosomal escape of siRNA effectively due to the pH-responsive disassem...
Source: Biomaterials - June 14, 2014 Category: Materials Science Authors: Xie Y, Qiao H, Su Z, Chen M, Ping Q, Sun M Tags: Biomaterials Source Type: research

Actively-targeted polyion complex micelles stabilized by cholesterol and disulfide cross-linking for systemic delivery of siRNA to solid tumors.
Abstract For small interfering RNA (siRNA)-based cancer therapies, we report an actively-targeted and stabilized polyion complex micelle designed to improve tumor accumulation and cancer cell uptake of siRNA following systemic administration. Improvement in micelle stability was achieved using two stabilization mechanisms; covalent disulfide cross-linking and non-covalent hydrophobic interactions. The polymer component was designed to provide disulfide cross-linking and cancer cell-targeting cyclic RGD peptide ligands, while cholesterol-modified siRNA (Chol-siRNA) provided additional hydrophobic stabilization to t...
Source: Biomaterials - June 12, 2014 Category: Materials Science Authors: Oe Y, Christie RJ, Naito M, Low SA, Fukushima S, Toh K, Miura Y, Matsumoto Y, Nishiyama N, Miyata K, Kataoka K Tags: Biomaterials Source Type: research

Matrix metalloproteinase 2-responsive micelle for siRNA delivery.
Abstract Systemic delivery of small interfering RNA (siRNA) into cancer cells remains the major obstacle to siRNA drug development. An ideal siRNA delivery vehicle for systemic administration should have long circulation time in blood, accumulate at tumor site, and sufficiently internalize into cancer cells for high-efficiency of gene silence. Herein, we report a core-shell Micelleplex delivery system that made from block copolymer bearing poly(ethylene glycol) (PEG), matrix metalloproteinase 2 (MMP-2)-degradable peptide PLG*LAG, cationic cell penetrating peptide polyarginine r9 and poly(ε-caprolactone) (PCL) for...
Source: Biomaterials - June 11, 2014 Category: Materials Science Authors: Wang HX, Yang XZ, Sun CY, Mao CQ, Zhu YH, Wang J Tags: Biomaterials Source Type: research

Cardiac RNAi therapy using RAGE siRNA/deoxycholic acid-modified polyethylenimine complexes for myocardial infarction.
Abstract Inflammatory response in myocardial ischemia-reperfusion injury plays a critical role in ventricular remodeling. To avoid deleterious effects of overwhelming inflammation, we blocked the expression of receptor for advanced glycation end-products (RAGE), a key mediator of the local and systemic inflammatory responses, via RNAi mechanism. Herein, a facial amphipathic deoxycholic acid-modified low molecular weight polyethylenimine (DA-PEI) was used as a siRNA delivery carrier to myocardium. The DA-PEI conjugate formed a stable complex with siRNA via electrostatic and hydrophobic interactions. The siRAGE/DA-P...
Source: Biomaterials - June 7, 2014 Category: Materials Science Authors: Hong J, Ku SH, Lee MS, Jeong JH, Mok H, Choi D, Kim SH Tags: Biomaterials Source Type: research

Therapeutic effect of a multi-targeted imidazolium compound in hepatocellular carcinoma.
Abstract Hepatocellular carcinoma (HCC) is one of the most commonly diagnosed lethal cancers in the world. We previously showed two imidazolium salts (IBN-1 and IBN-9) with a moderate efficacy for HCC. Here we report a more potent imidazolium compound IBN-65 (1-benzyl-2-phenyl-3-(4-isopropyl)-benzyl-imidazolium chloride) and the associated mechanisms of action in a mouse model of HCC. The IC50 of this compound in various liver cancer cell lines was around 5 μm. IBN-65 dose-dependently arrested cell cycle at G1 phase and was associated with the down-regulation of the cyclin-dependent kinase-4, -6, cyclin D1, and ...
Source: Biomaterials - June 6, 2014 Category: Materials Science Authors: Gopalan B, Narayanan K, Ke Z, Lu T, Zhang Y, Zhuo L Tags: Biomaterials Source Type: research

Tumor targeting RGD conjugated bio-reducible polymer for VEGF siRNA expressing plasmid delivery.
Abstract Targeted delivery of therapeutic genes to the tumor site is critical for successful and safe cancer gene therapy. The arginine grafted bio-reducible poly (cystamine bisacrylamide-diaminohexane, CBA-DAH) polymer (ABP) conjugated poly (amido amine) (PAMAM), PAM-ABP (PA) was designed previously as an efficient gene delivery carrier. To achieve high efficacy in cancer selective delivery, we developed the tumor targeting bio-reducible polymer, PA-PEG1k-RGD, by conjugating cyclic RGDfC (RGD) peptides, which bind αvβ3/5 integrins, to the PAM-ABP using polyethylene glycol (PEG, 1 kDa) as a spacer. Physical cha...
Source: Biomaterials - May 31, 2014 Category: Materials Science Authors: Kim HA, Nam K, Kim SW Tags: Biomaterials Source Type: research

Direct cytosolic siRNA delivery by reconstituted high density lipoprotein for target-specific therapy of tumor angiogenesis.
We described here the mechanisms by which small interfering RNA (siRNA) molecules incorporated in reconstituted high density lipoprotein (rHDL) were efficiently transferred into the cytoplasm of cells to perform target-specific therapy of tumor angiogenesis. Using fluorescent-tagged apolipoprotein A-I (apoA-I) and cholesterol-conjugated siRNA (Chol-siRNA), it was confirmed with FACS and confocal microscopic measurements that Chol-siRNA-loaded rHDL nanoparticles (rHDL/Chol-siRNA complexes) were successfully established and apoA-I certainly was attached to the surface of Chol-siRNA-loaded lipoplexes (Lipos/Chol-siRNA complex...
Source: Biomaterials - May 27, 2014 Category: Materials Science Authors: Ding Y, Wang Y, Zhou J, Gu X, Wang W, Liu C, Bao X, Wang C, Li Y, Zhang Q Tags: Biomaterials Source Type: research

Molecular modeling of polynucleotide complexes.
Abstract Delivery of polynucleotides into patient cells is a promising strategy for treatment of genetic disorders. Gene therapy aims to either synthesize desired proteins (DNA delivery) or suppress expression of endogenous genes (siRNA delivery). Carriers constitute an important part of gene therapeutics due to limitations arising from the pharmacokinetics of polynucleotides. Non-viral carriers such as polymers and lipids protect polynucleotides from intra and extracellular threats and facilitate formation of cell-permeable nanoparticles through shielding and/or bridging multiple polynucleotide molecules. Format...
Source: Biomaterials - May 21, 2014 Category: Materials Science Authors: Meneksedag-Erol D, Tang T, Uludağ H Tags: Biomaterials Source Type: research

Tumor-specific delivery of siRNA using supramolecular assembly of hyaluronic acid nanoparticles and 2b RNA-binding protein/siRNA complexes.
Abstract Anticancer therapeutics delivering exogenous siRNA have been explored to suppress the tumor-associated genes, but several limitations of siRNA delivery such as tumor-targeted delivery, controlled siRNA release at the sites of interest, or instabilities of siRNA in physiological fluids should be preferentially addressed for its clinical applications. As an attempt to meet these criteria, we designed a supramolecular assembly, which was composed of cholesterol-bearing hyaluronic acid (HA-Chol) conjugates and 2b RNA-binding protein (2b)/siRNA complexes. In contrast to the traditional siRNA polyplexes using e...
Source: Biomaterials - May 19, 2014 Category: Materials Science Authors: Choi KM, Jang M, Kim JH, Ahn HJ Tags: Biomaterials Source Type: research

Sustained localized presentation of RNA interfering molecules from in situ forming hydrogels to guide stem cell osteogenic differentiation.
Abstract To date, RNA interfering molecules have been used to differentiate stem cells on two-dimensional (2D) substrates that do not mimic three-dimensional (3D) microenvironments in the body. Here, in situ forming poly(ethylene glycol) (PEG) hydrogels were engineered for controlled, localized and sustained delivery of RNA interfering molecules to differentiate stem cells encapsulated within the 3D polymer network. RNA interfering molecules were released from the hydrogels in a sustained and controlled manner over the course of 3-6 weeks, and exhibited high bioactivity. Importantly, it was demonstrated that the d...
Source: Biomaterials - May 12, 2014 Category: Materials Science Authors: Nguyen MK, Jeon O, Krebs MD, Schapira D, Alsberg E Tags: Biomaterials Source Type: research

SiRNA-phospholipid conjugates for gene and drug delivery in cancer treatment.
In this study, the thiol-modified sense and antisense siRNA are chemically conjugated with phospholipids to form sense and antisense siRNA-phospholipid, and then these sense or antisense siRNA-phospholipids with equal amounts are annealed to generate siRNA-phospholipids. The siRNA-phospholipids can serve dual functions as agents that can silence gene expression and as a component of nanoparticles to embed hydrophobic anticancer drugs to cure tumor. siRNA-phospholipids together with cationic lipids and DSPE-PEG2000 fuse around PLGA to form siRNA-phospholipids enveloped nanoparticles (siRNA-PCNPs), which can deliver siRNAs a...
Source: Biomaterials - May 2, 2014 Category: Materials Science Authors: Liu H, Li Y, Mozhi A, Zhang L, Liu Y, Xu X, Xing J, Liang X, Ma G, Yang J, Zhang X Tags: Biomaterials Source Type: research

Low-density lipoprotein-coupled N-succinyl chitosan nanoparticles co-delivering siRNA and doxorubicin for hepatocyte-targeted therapy.
In this study, low-density lipoprotein (LDL) was isolated from human plasma and loaded with cholesterol-conjugated siRNA to silence the multidrug resistant gene of tumors. Chol-siRNA/LDL-coupled N-succinyl chitosan nanoparticles loaded with doxorubicin (Dox-siRNA/LDL-SCS-NPs) were then prepared and characterised. The Dox-siRNA/LDL-SCS-NPs had average particle size of 206.4 ± 9.2 nm, entrapment efficiency of 71.06% ± 1.42%, and drug-loading amount of 12.35% ± 0.87%. In vitro antitumor activity revealed that cell growth was significantly inhibited. The accumulation of Dox by fluorescence microscopy and flow cytome...
Source: Biomaterials - April 24, 2014 Category: Materials Science Authors: Zhu QL, Zhou Y, Guan M, Zhou XF, Yang SD, Liu Y, Chen WL, Zhang CG, Yuan ZQ, Liu C, Zhu AJ, Zhang XN Tags: Biomaterials Source Type: research