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Polymeric nanoparticles of siRNA prepared by a double-emulsion solvent-diffusion technique: Physicochemical properties, toxicity, biodistribution and efficacy in a mammary carcinoma mice model.
Abstract siRNA-loaded nanoparticles (NPs) administered systemically can overcome the poor stability and rapid elimination of free double-stranded RNA in circulation, resulting in increased tumor accumulation and efficacy. siRNA against osteopontin (siOPN), a protein involved in breast cancer development, was encapsulated in poly(D,L-lactic-co-glycolic acid) NPs by a double emulsion solvent diffusion (DESD) technique. We also compared the effect of polyethylenimine (PEI) molecular weight (800 Da and 25 kDa), used as the counter-ion for siRNA complexation, on the physicochemical properties of the NPs, cytotoxicity...
Source: Biomaterials - August 23, 2017 Category: Materials Science Authors: Ben David-Naim M, Grad E, Aizik G, Nordling-David MM, Moshel O, Granot Z, Golomb G Tags: Biomaterials Source Type: research

Co-delivery of platinum drug and siNotch1 with micelleplex for enhanced hepatocellular carcinoma therapy.
Abstract As part of HCC tumor cellularity, cancer stem cells (CSCs) are considered a major obstacle to eradicate hepatocellular carcinoma (HCC), which is the third most common cause of cancer-related death worldwide, and the accumulation of chemotherapeutic drug-resistant CSCs invariably accounts for poor prognosis and HCC relapse. In the present study, we explored the efficacy of co-delivery of platinum drug and siRNA targeting Notch1 to treat CSCs-harboring HCC. To overcome the challenging obstacles of platinum drug and siRNA in the systemic administration, we developed a micellar nanoparticle (MNP) to deliver p...
Source: Biomaterials - August 17, 2015 Category: Materials Science Authors: Shen S, Sun CY, Du XJ, Li HJ, Liu Y, Xia JX, Zhu YH, Wang J Tags: Biomaterials Source Type: research

Enhanced antitumor efficacies of multifunctional nanocomplexes through knocking down the barriers for siRNA delivery.
Abstract Multifunctional nanocomplexes (NCs) consisting of urocanic acid-modified galactosylated trimethyl chitosan (UA-GT) conjugates as polymeric vectors, poly(allylamine hydrochloride)-citraconic anhydride (PAH-Cit) as charge-reversible crosslinkers, and vascular endothelial growth factor (VEGF) siRNA as therapeutic genes, were rationally designed to simultaneously overcome the extracellular, cellular, and intracellular barriers for siRNA delivery. The strong physical stability of UA-GT/PAH-Cit/siRNA NCs (UA-GT NCs) at pH 7.4 and 6.5 endowed protection from massive dilution, competitive ions, and ubiquitous nuc...
Source: Biomaterials - February 1, 2015 Category: Materials Science Authors: Han L, Tang C, Yin C 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-penetrating codelivery of siRNA and paclitaxel with ultrasound-responsive nanobubbles hetero-assembled from polymeric micelles and liposomes.
Abstract Drug resistance is a big problem in systemic chemotherapy of hepatocellular carcinoma (HCC), and nanomedicines loaded with both chemotherapeutic agents (e.g. paclitaxel, PTX) and siRNA's targeting antiapoptosis genes (e.g. BCL-2) possess the advantages to simultaneously overcome the efflux pump-mediated drug resistance and antiapoptosis-related drug resistance. However, tumor-penetrating drug delivery with this type of nanomedicines is extremely difficult due to their relatively big size compared to the single drug-loaded nanomedicines. Aiming at address this problem, US-responsive nanobubbles encapsulati...
Source: Biomaterials - April 17, 2014 Category: Materials Science Authors: Yin T, Wang P, Li J, Wang Y, Zheng B, Zheng R, Cheng D, Shuai X Tags: Biomaterials Source Type: research

Inhibition of hepatocellular carcinoma growth using immunoliposomes for co-delivery of adriamycin and ribonucleotide reductase M2 siRNA.
Abstract The chemotherapy combined with gene therapy has received great attention. We developed targeted LPD (liposome-polycation-DNA complex) conjugated with anti-EGFR (epidermal growth factor receptor) Fab' co-delivering adriamycin (ADR) and ribonucleotide reductase M2 (RRM2) siRNA (ADR-RRM2-TLPD), to achieve combined therapeutic effects in human hepatocellular carcinoma (HCC) overexpressing EGFR. The antitumor activity and mechanisms of ADR-RRM2-TLPD were investigated. The results showed that RRM2 expression was higher in HCC than in non-HCC tissue, and RRM2 siRNA inhibited HCC cell proliferation, suggesting th...
Source: Biomaterials - September 20, 2013 Category: Materials Science Authors: Gao J, Chen H, Yu Y, Song J, Song H, Su X, Li W, Tong X, Qian W, Wang H, Dai J, Guo Y Tags: Biomaterials Source Type: research