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Source: Biomaterials

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Total 156 results found since Jan 2013.

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

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

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

Enhanced silencing and stabilization of siRNA polyplexes by histidine-mediated hydrogen bonds.
Abstract Branched peptides containing histidines and lysines (HK) have been shown to be effective carriers for DNA and siRNA. We anticipate that elucidation of the binding mechanism of HK with siRNA will provide greater insight into the self-assembly and delivery of the HK:siRNA polyplex. Non-covalent bonds between histidine residues and nucleic acids may enhance the stability of siRNA polyplexes. We first compared the polyplex biophysical properties of a branched HK with those of branched asparagine-lysine peptide (NK). Consistent with siRNA silencing experiments, gel electrophoresis demonstrated that the HK siRN...
Source: Biomaterials - October 22, 2013 Category: Materials Science Authors: Chou ST, Hom K, Zhang D, Leng Q, Tricoli LJ, Hustedt JM, Lee A, Shapiro MJ, Seog J, Kahn JD, Mixson AJ Tags: Biomaterials Source Type: research

Self-crosslinked human serum albumin nanocarriers for systemic delivery of polymerized siRNA to tumors.
In this study, we utilized human serum albumin (HSA), which is the most abundant of the plasma proteins, as a siRNA carrier for systemic tumor-targeted siRNA delivery. Both HSA and siRNA molecules were thiol-introduced to improve the binding affinity for each other. The resulting thiolated HSA (tHSA) and polymerized siRNA (psi) formed stable nanosized complexes (psi-tHSAs) by chemical crosslinking and self-crosslinking. After internalization, the psi-tHSAs showed target gene silencing activity in vitro comparable to conventional Lipofectamine™-siRNA complexes, without remarkable cytotoxicity. After intravenous injection...
Source: Biomaterials - September 16, 2013 Category: Materials Science Authors: Son S, Song S, Lee SJ, Min S, Kim SA, Yhee JY, Huh MS, Chan Kwon I, Jeong SY, Byun Y, Kim SH, Kim K Tags: Biomaterials Source Type: research

Core-Shell type lipid/rPAA-Chol polymer hybrid nanoparticles for in vivo siRNA delivery.
In this study, the core-shell type lipid/rPAA-Chol hybrid nanoparticles (PEG-LP/siRNA NPs and T7-LP/siRNA NPs) were developed for improving in vivo siRNA delivery by modifying the surface of rPAA-Chol/siRNA nanoplex core with a lipid shell, followed by post-insertion of polyethylene glycol phospholipid (DSPE-PEG) and/or peptide (HAIYPRH, named as T7) modified DSPE-PEG-T7. The integrative hybrid nanostructures of LP/siRNA NPs were evidenced by dynamic light scattering (DLS), confocal laser scanning microscope (CLSM), cryo-transmission electron microscope (Cryo-TEM) and surface plasmon resonance (SPR) assay. It was demonstr...
Source: Biomaterials - December 5, 2013 Category: Materials Science Authors: Gao LY, Liu XY, Chen CJ, Wang JC, Feng Q, Yu MZ, Ma XF, Pei XW, Niu YJ, Qiu C, Pang WH, Zhang Q Tags: Biomaterials Source Type: research

In vivo disassembly of IV administered siRNA matrix nanoparticles at the renal filtration barrier.
In this report, the biodistribution in mice of siRNA loaded dextran nanogels was investigated in detail. Both single photon emission computed tomography (SPECT) imaging and fluorescence single particle tracking (fSPT) indicate that the particles are rapidly cleared from the circulation. PEGylation of the nanogels was not able to increase the half-life in the bloodstream. Carrier disassembly in the systemic circulation and phagocytic clearance are known to facilitate the elimination of siRNA nanoparticles. Additionally, it is demonstrated for dextran nanogels that also the kidneys play an important role in their elimination...
Source: Biomaterials - December 19, 2012 Category: Materials Science Authors: Naeye B, Deschout H, Caveliers V, Descamps B, Braeckmans K, Vanhove C, Demeester J, Lahoutte T, De Smedt SC, Raemdonck K Tags: Biomaterials Source Type: research

Cellular internalization and gene silencing of siRNA polyplexes by cytocleavable cationic polyrotaxanes with tailored rigid backbones.
Abstract To achieve successful delivery of siRNA therapeutics, cytocleavable cationic polyrotaxanes (PRXs) composed of N,N-dimethylaminoethyl (DMAE) group-modified α-cyclodextrins (CDs) that were threaded onto a poly(ethylene glycol) (PEG) axis and capped with a bulky stopper using cytocleavable disulfide linkages (DMAE-PRX) were utilized as an siRNA carrier. DMAE-PRXs with various numbers of threading CDs and modified DMAE groups were synthesized, and the physicochemical properties, cellular internalization, and gene silencing activity of DMAE-PRX/siRNA were investigated to elucidate the relationship between its...
Source: Biomaterials - January 30, 2013 Category: Materials Science Authors: Tamura A, Yui N 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

Controlled and sustained delivery of siRNA/NPs from hydrogels expedites bone fracture healing.
Abstract Despite great potential, delivery remains as the most significant barrier to the widespread use of siRNA therapeutics. siRNA has delivery limitations due to susceptibility to RNase degradation, low cellular uptake, and poor tissue-specific localization. Here, we report the development of a hybrid nanoparticle (NP)/hydrogel system that overcomes these challenges. Hydrogels provide localized and sustained delivery via controlled release of entrapped siRNA/NP complexes while NPs protect and enable efficient cytosolic accumulation of siRNA. To demonstrate therapeutic efficacy, regenerative siRNA against WW do...
Source: Biomaterials - June 4, 2017 Category: Materials Science Authors: Wang Y, Malcolm DW, Benoit DSW Tags: Biomaterials Source Type: research

Interleukin-4 receptor-targeted delivery of Bcl-xL siRNA sensitizes tumors to chemotherapy and inhibits tumor growth.
In this study, we exploited IL-4R-targeted delivery of Bcl-xL siRNA to IL-4R-expressing tumor cells in order to sensitize them to chemotherapy. To target IL-4R, an IL-4R-binding peptide, IL4RPep-1, was attached to branched polyethyleneimine-superparamagnetic iron oxide nanoparticles (BPEI-SPION). These nanoparticles were then complexed with Bcl-xL-targeting siRNA. IL-4R-targeted BPEI-SPION/Bcl-xL siRNA more efficiently reduced Bcl-xL gene expression and enhanced cytotoxicity of doxorubicin in MDA-MB231 breast tumor cells compared to untargeted BPEI-SPION/Bcl-xL siRNA. The siRNA was released from the complexes after 15 h o...
Source: Biomaterials - July 15, 2017 Category: Materials Science Authors: Guruprasath P, Kim J, Gunassekaran GR, Chi L, Kim S, Park RW, Kim SH, Baek MC, Bae SM, Kim SY, Kim DK, Park IK, Kim WJ, Lee B Tags: Biomaterials Source Type: research

Dexamethasone-conjugated polyethylenimine/MIF siRNA complex regulation of particulate matter-induced airway inflammation.
Abstract Inhalation of airborne particulate matter (PM), such as silicon dioxide (SiO2) and titanium dioxide (TiO2), induces acute lung inflammation. siRNA therapy has been proposed as a method to repair acute lung inflammation. To determine whether DEXA-PEI/MIF siRNA contributes to SiO2-induced acute lung inflammation repair, we administered Dexa-PEI/MIF siRNA in SiO2-treated Beas-2b cells and instilled DEXA-PEI-MIF siRNA intratracheally in mice with SiO2-induced acute lung inflammation. Using genetic (MIF mRNA RT-PCR), histological (H&E and PAS) and immunohistochemical (MIF and Muc5ac) analyses, we estimated...
Source: Biomaterials - July 4, 2013 Category: Materials Science Authors: Choi M, Lee M, Rhim T 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

Restoration of chemosensitivity by multifunctional micelles mediated by P-gp siRNA to reverse MDR.
Abstract One of the main obstacles in tumor therapy is multiple drug resistance (MDR) and an underlying mechanism of MDR is up-regulation of the transmembrane ATP-binding cassette (ABC) transporter proteins, especially P-glycoprotein (P-gp). In the synergistic treatment of siRNA and anti-cancer drug doxorubicin, it is crucial that both the siRNA and doxorubicin are simultaneously delivered to the tumor cells and the siRNA can fleetly down-regulate P-g before doxorubicin inactivates the P-gp and is pumped out. Herein, a type of micelles comprising a polycationic PEI-CyD shell to condense the siRNA and hydrophobic c...
Source: Biomaterials - July 4, 2014 Category: Materials Science Authors: Shen J, Wang Q, Hu Q, Li Y, Tang G, Chu PK Tags: Biomaterials Source Type: research

Dual-responsive polyplexes with enhanced disassembly and endosomal escape for efficient delivery of siRNA.
Abstract Despite the extracellular barriers for siRNA delivery have been overcome by utilizing advanced nanoparticle delivery systems, the key intracellular barriers after internalization including efficient disassembly of siRNA and endosomal escape still remains challenging. To address the issues, we developed a unique pH- and redox potential-responsive polyplex delivery system based on the copolymer of mPEG-b-PLA-PHis-ssPEI1.8 k, which is composed of a pH-responsive copolymer of PEG-b-PLA-PHis (Mw 5 k) and a branched PEI (Mw1.8 k) linked with redox cleavable disulfide bond. The copolymer showed excellent s...
Source: Biomaterials - February 3, 2018 Category: Materials Science Authors: Zhu J, Qiao M, Wang Q, Ye Y, Ba S, Ma J, Hu H, Zhao X, Chen D Tags: Biomaterials Source Type: research