Wednesday, June 11, 2014

PLGA for use in miRNA delivery as cancer therapy

PolySciTech (www.polyscitech.com) provides a wide array of PLGA and PEG-PLGA type block copolymers. These types of polymers have been utilized for delivery of microRNAs, which are small non-coding RNA’s that affect gene expression in cancer cells, for treatement of cancer. A recent review article provides an excellent overview of this field. Read more: Chen, Yunching, Dong-Yu Gao, and Leaf Huang. "In Vivo Delivery of miRNAs For Cancer Therapy: Challenges and Strategies." Advanced drug delivery reviews (2014). http://www.sciencedirect.com/science/article/pii/S0169409X14001033

“Abstract: MicroRNAs (miRNAs), small non-coding RNAs, can regulate post-transcriptional gene expressions and silence a broad set of target genes. miRNAs, aberrantly expressed in cancer cells, play an important role in modulating gene expressions, thereby regulating downstream signaling pathways and affecting cancer formation and progression. Oncogenes or tumor suppressor genes regulated by miRNAs mediate cell cycle progression, metabolism, cell death, angiogenesis, metastasis and immunosuppression in cancer. Recently, miRNAs have emerged as therapeutic targets or tools and biomarkers for diagnosis and therapy monitoring in cancer. Since miRNAs can regulate multiple cancer-related genes simultaneously, using miRNAs as a therapeutic approach plays an important role in cancer therapy. However, one of the major challenges of miRNA-based cancer therapy is to achieve specific, efficient and safe systemic delivery of therapeutic miRNAs in vivo. This review discusses the key challenges to the development of the carriers for miRNA-based therapy and explores current strategies to systemically deliver miRNAs to cancer without induction of toxicity. Abbreviations: AAVs, adeno-associated viruses; AEBP1, adipocyte enhancer-binding protein 1; AEG-1, astrocyte elevated gene-1; Ago, argonaute protein; Ago2, argonaute2 protein; AMOs, anti-miRNA oligonucleotides; BBB, blood–brain-barrier; CDK6, cyclin-dependent protein kinase 6; CLL, chronic lymphocytic leukemia; CSC, cancer stem cells; DCs, dendritic cells; dsRNAs, short double strand RNAs; ECM, extracellular matrix; EGFR, epidermal growth factor receptor; EMT, epithelial–mesenchymal transition; EPR, enhanced permeability and retention; FGF, fibroblast growth factor; GBM, glioblastoma multiforme; HCC, hepatocellular carcinoma; HCV, hepatitis c virus; HDL, high-density lipoprotein; HIF-α, hypoxia-inducible factor-α; IFN, type I interferon; IL, interleukin; LAC, lung adenocarcinoma; LNA, locked nucleic acid; LPH, liposome–polycation–hyaluronic acid; mAbs, monoclonal antibodies; MCL1, myeloid cell leukemia sequence 1; MDSCs, myeloid-derived suppressor cells; miRNA, microRNA; NPs, nanoparticles; NSCLC, non-small-cell lung cancer; PEG, polyethylene glycol; PEI, polyethyleneimine; PLGA, poly(lactide-co-glycolide); pre-miRNAs, hairpin-forming miRNA precursors; pri-miRNAs, long RNA primary transcripts; PU, polyurethane; RES, reticuloendothelial system; RISC, RNA-induced silencing complex; scFv, single-chain variable fragment; siRNA, short interfering RNA; SLNs, solid lipid nanoparticles; SNA-NCs, spherical nucleic acid nanoparticle conjugates; SPARC, secreted protein acidic and rich in cysteine; TLRs, Toll-like receptors; TNF, tumor necrosis factor; VEGF, vascular endothelial growth factor. Keywords: miRNA; Gene delivery; In vivo delivery; Cancer therapy; Nanotechnology”

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