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Source: Biomaterials

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Total 156 results found since Jan 2013.

Delivery of siRNA to the brain using a combination of nose-to-brain delivery and cell-penetrating peptide-modified nano-micelles.
In this study, we describe intranasal brain delivery of siRNA or dextran (Mw: 10,000 Da) as a model siRNA, by using MPEG-PCL-Tat. Intranasal delivery of dextran with MPEG-PCL-Tat improved brain delivery compared to intravenous delivery of dextran either with or without MPEG-PCL-Tat. We also studied the intranasal transfer of MPEG-PCL-Tat to the brain via the olfactory and trigeminal nerves, the putative pathways to the brain from the nasal cavity. We found that MPEG-PCL-Tat accelerated transport along the olfactory and trigeminal nerve pathway because of its high permeation across the nasal mucosa. PMID: 23992922 [Pu...
Source: Biomaterials - August 28, 2013 Category: Materials Science Authors: Kanazawa T, Akiyama F, Kakizaki S, Takashima Y, Seta Y Tags: Biomaterials Source Type: research

Combinational delivery of c-myc siRNA and nucleoside analogs in a single, synthetic nanocarrier for targeted cancer therapy.
In this study, we developed a Lipid/Calcium/Phosphate (LCP) nanoparticle that combines chemotherapy with gene therapy. By encapsulating a chemodrug, gemcitabine monophosphate (GMP), and siRNA specific to the undruggable cMyc oncogene (cMyc siRNA) into a single nano-sized vesicle and systemically administering them to nude mice, we achieved potent anti-tumor activity in both subcutaneous and orthotopic models of NSCLC. The improvements in therapeutic response over either cMyc siRNA or GMP therapy alone, were demonstrated by the ability to effectively induce the apoptosis of tumor cells and the significant reduction of proli...
Source: Biomaterials - August 8, 2013 Category: Materials Science Authors: Zhang Y, Peng L, Mumper RJ, Huang L Tags: Biomaterials Source Type: research

Click conjugated polymeric immuno-nanoparticles for targeted siRNA and antisense oligonucleotide delivery.
Abstract Efficient and targeted cellular delivery of small interfering RNAs (siRNAs) and antisense oligonucleotides (AONs) is a major challenge facing oligonucleotide-based therapeutics. The majority of current delivery strategies employ either conjugated ligands or oligonucleotide encapsulation within delivery vehicles to facilitate cellular uptake. Chemical modification of the oligonucleotides (ONs) can improve potency and duration of activity, usually as a result of improved nuclease resistance. Here we take advantage of innovations in both polymeric delivery vehicles and ON stabilization to achieve receptor-me...
Source: Biomaterials - August 7, 2013 Category: Materials Science Authors: Chan DP, Deleavey GF, Owen SC, Damha MJ, Shoichet MS Tags: Biomaterials Source Type: research

Albumin-based nanoconjugates for targeted delivery of therapeutic oligonucleotides.
Abstract Nanoparticle-based delivery has become an important strategy to advance siRNA and antisense oligonucleotides into clinical reality. However, limited biodistribution of nanoparticles and the toxicity of some nanocarriers restrict the wider application of this strategy. To address these issues we aimed to construct oligonucleotide delivery systems which are non-cytotoxic and smaller than typical nanoparticles. Thus, a morpholino oligonucleotide was conjugated to a tumor-targeting RGD peptide, and then, multiple RGD-oligo conjugates were linked to a single molecule of human serum albumin via a reductively re...
Source: Biomaterials - July 19, 2013 Category: Materials Science Authors: Ming X, Carver K, Wu L Tags: Biomaterials Source Type: research

Delivery of Nox2-NADPH oxidase siRNA with polyketal nanoparticles for improving cardiac function following myocardial infarction.
This study highlights the potential of polyketals as siRNA delivery vehicles to the MI heart and represents a viable therapeutic approach for targeting oxidative stress. PMID: 23856052 [PubMed - as supplied by publisher]
Source: Biomaterials - July 12, 2013 Category: Materials Science Authors: Somasuntharam I, Boopathy AV, Khan RS, Martinez MD, Brown ME, Murthy N, Davis ME Tags: Biomaterials Source Type: research

In vivo tumor targeting via nanoparticle-mediated therapeutic siRNA coupled to inflammatory response in lung cancer mouse models.
In this study, we report the use of siRNA/RGD gold nanoparticles capable of targeting tumor cells in a lung cancer syngeneic orthotopic murine model. Therapeutic RGD-nanoparticle treatment resulted in successful targeting evident from significant c-myc oncogene down-regulation followed by tumor growth inhibition and prolonged survival of lung tumor bearing mice, possibly via αvβ3 integrin interaction. Our results suggest that RGD gold nanoparticles-mediated delivery of siRNA by intratracheal instillation in mice leads to successful suppression of tumor cell proliferation and respective tumor size reduction. These results...
Source: Biomaterials - July 12, 2013 Category: Materials Science Authors: Conde J, Tian F, Hernández Y, Bao C, Cui D, Janssen KP, Ibarra MR, Baptista PV, Stoeger T, de la Fuente JM 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

Heat shock protein-mediated cell penetration and cytosolic delivery of macromolecules by a telomerase-derived peptide vaccine.
Abstract A reverse-transcriptase-subunit of telomerase (hTERT) derived peptide, GV1001, has been developed as a vaccine against various cancers. Here, we report an unexpected function of GV1001 as a cell-penetrating peptide (CPP). GV1001 was delivered into a variety of cells including various cancer cell lines and primary blood cells. Moreover, the delivered GV1001 was predominantly located in the cytoplasm of the cells, while a significantly higher proportion of TAT peptide was localized in the nucleus. Macromolecules such as proteins, DNA and siRNA, which were linked to GV1001 by direct covalent conjugation or n...
Source: Biomaterials - July 1, 2013 Category: Materials Science Authors: Lee SA, Kim BR, Kim BK, Kim DW, Shon WJ, Lee NR, Inn KS, Kim BJ Tags: Biomaterials Source Type: research

Mannosylated bioreducible nanoparticle-mediated macrophage-specific TNF-α RNA interference for IBD therapy.
Abstract The application of RNA interference (RNAi) for inflammatory bowel disease (IBD) therapy has been limited by the lack of non-cytotoxic, efficient and targetable small interfering RNA (siRNA) carriers. TNF-α is the major pro-inflammatory cytokine mainly secreted by macrophages during IBD. Here, a mannosylated bioreducible cationic polymer (PPM) was synthesized and further spontaneously assembled nanoparticles (NPs) assisted by sodium triphosphate (TPP). The TPP-PPM/siRNA NPs exhibited high uniformity (polydispersity index = 0.004), a small particle size (211-275 nm), excellent bioreducibility, and enha...
Source: Biomaterials - June 29, 2013 Category: Materials Science Authors: Xiao B, Laroui H, Ayyadurai S, Viennois E, Charania MA, Zhang Y, Merlin D Tags: Biomaterials Source Type: research

PSA-responsive and PSMA-mediated multifunctional liposomes for targeted therapy of prostate cancer.
In this study, we constructed a dual-modified liposome that incorporated PSA-responsive and PSMA-mediated liposomes and potentially offers double selectivity for PC. The folate moiety binds quickly to PSMA-positive tumors, and the PSA-responsive moiety is cleaved by PSA that was enriched in tumor tissues. The activated liposomes (folate and cell-penetrating peptides dual-modifications) are subsequently taken up by the tumor cells via polyarginine's penetrating effects and receptor-mediated endocytosis. To corroborate these assumptions, a series of experiments were conducted, including PSA-responsive peptide hydrolysis kine...
Source: Biomaterials - June 15, 2013 Category: Materials Science Authors: Xiang B, Dong DW, Shi NQ, Gao W, Yang ZZ, Cui Y, Cao DY, Qi XR Tags: Biomaterials Source Type: research

Integrin binding and MAPK signal pathways in primary cell responses to surface chemistry of calcium silicate cements.
This study sheds light on the mechanism by which the modulation of the chemical composition of calcium silicate cements with different Si/Ca molar ratios could produce different cell responses. Two primary cell types (human mesenchymal stem cells (hMSCs) and human dental pulp cells (hDPCs)) were used to elicit the changes in total DNA content, integrin subunit levels, phosphor-focal adhesion kinase (pFAK) levels, and mitogen-activated protein kinase (MAPK) signaling pathway activity at the cell attachment stage. The effect of small interfering RNA (siRNA) transfection targeting collagen type I (COL I) and fibronectin (FN) ...
Source: Biomaterials - June 13, 2013 Category: Materials Science Authors: Shie MY, Ding SJ Tags: Biomaterials Source Type: research

Trilayer micelles for combination delivery of rapamycin and siRNA targeting Y-box binding protein-1 (siYB-1).
In this study, it has been shown that PCL can encapsulate RAP with high loading efficiencies, and PAsp(DET) can successfully interact with siRNA for efficient transfection/knockdown with negligible cytotoxicity. The enhanced therapeutic efficacy of RAP/siYB-1 micelles was demonstrated in cell cultures and in a PC3 xenograft nude mouse model of human prostate cancer. Herein, we demonstrate that trilayer micelles are a promising approach to improve the simultaneous delivery of combination siRNA/drug therapies. PMID: 23768780 [PubMed - as supplied by publisher]
Source: Biomaterials - June 11, 2013 Category: Materials Science Authors: Zeng S, Xiong MP Tags: Biomaterials Source Type: research

A review of the current status of siRNA nanomedicines in the treatment of cancer.
Abstract RNA interference currently offers new opportunities for gene therapy by the specific extinction of targeted gene(s) in cancer diseases. However, the main challenge for nucleic acid delivery still remains its efficacy through intravenous administration. Over the last decade, many delivery systems have been developed and optimized to encapsulate siRNA and to specifically promote their delivery into tumor cells and improve their pharmacokinetics for anti-cancer purposes. This review aims to sum up the potential targets in numerous pathways and the properties of recently optimized siRNA synthetic nanomedicine...
Source: Biomaterials - May 30, 2013 Category: Materials Science Authors: Resnier P, Montier T, Mathieu V, Benoit JP, Passirani C Tags: Biomaterials Source Type: research

Imaging and therapy of liver fibrosis using bioreducible polyethylenimine/siRNA complexes conjugated with N-acetylglucosamine as a targeting moiety.
Abstract Diagnosis and therapy of early stage liver fibrosis is very important for the treatment of fatal liver diseases. Here, we report on the targeted imaging and therapy of activated hepatic stellate cells (HSCs) and fibrotic liver tissue using N-acetylglucosamine (GlcNAc)- and indocyanine green (ICG)-conjugated PEI/siRNA complexes. The conjugation of a disulfide bond to PEI (PEI-D) was achieved by Michael addition. We modified PEI with N-acetylglucosamine (PEI-D-GlcNAc), which can specifically interact with desmin on activated HSCs, using the EDC coupling method. Confocal microscopic analysis showed that the ...
Source: Biomaterials - May 28, 2013 Category: Materials Science Authors: Kim SJ, Ise H, Kim E, Goto M, Akaike T, Chung BH Tags: Biomaterials Source Type: research

A review of nanotechnological approaches for the prophylaxis of HIV/AIDS.
Abstract Successful treatment and control of HIV/AIDS is one of the biggest challenges of 21st century. More than 33 million individuals are infected with HIV worldwide and more than 2 million new cases of HIV infection have been reported. The situation demands development of effective prevention strategies to control the pandemic of AIDS. Due to lack of availability of an effective HIV vaccine, antiretroviral drugs and nucleic acid therapeutics like siRNA have been explored for HIV prophylaxis. Clinical trials shave shown that antiretroviral drugs, tenofovir and emtricitabine can offer some degree of HIV preventi...
Source: Biomaterials - May 28, 2013 Category: Materials Science Authors: Date AA, Destache CJ Tags: Biomaterials Source Type: research