Preparation and evaluation of a non-viral gene vector for SiRNA: Multifunctional envelope-type nano device

Abstract

We prepared and evaluated a multifunctional envelope-type nano device (MEND) as a liver-targeting and long-circulation carrier for SiRNA. The polymer GA-PEG-Pp-DOPE was synthesized by modifying polyethylene glycol (PEG) with glycyrrhetinic acid (GA), peptide (Pp), and dioleoyl phosphoethanolamine (DOPE). The Pp is a substrate of matrix metalloproteinase 2. MEND was prepared with GA-PEG-Pp-DOPE and cationic phospholipids by the filming-rehydration method, and the orthogonal test was applied to optimize the prescription. The results of the biological evaluation results suggest that MEND is a promising delivery system for SiRNA.

Protease-triggered bioresponsive drug delivery for the targeted theranostics of malignancy

“…Unsatisfactory in vivo efficacy limits the clinical transformation of widely used gene carriers such as lipoplex and polyplex. Against this disadvantage, nanotechnology has been skillfully used to construct various therapeutic gene delivery systems, typically such as PEG shielded MMP sensitive CPPs 101 , envelope-type non-viral nanodevice for liver-targeting siRNA delivery 102 , polyethylenimine (PEI)-based chlorotoxin-targeted melittin gene delivery to MMP-2 positive prostate cancer cells 103 , MMP-2-cleavable PEG- β -cyclodextrin-PEI nanoconjugates for tumor suppressor microRNA miR-34a-induced breast cancer treatment 104 , MMP-2-cleavable motif-included short amphiphilic peptide hydrogels for cell-demanded remedial peptide release into cervical cancer cells 105 , MMP-2-sensitive cytotoxic peptide‒dendrimer conjugates for enhanced intracellular enrichment, deep tumor penetration, promoted cell apoptosis and anti-glioblastoma (GBM) performance 106 , multifunctional fusion proteins for targeting the release of interferon gamma 107 , pro-apoptotic peptide 108 , or cytotoxic enediyne 109 into MMP-2-dysregulated tumor tissues. Moreover, some promising nanocomplexes were also developed for the co-delivery of heat shock protein 70-specific siRNA (siHSP70) and tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) 110 , sequentially responsive dual-targeted peptide presentation 111 , MMP-2/glutathione (GSH) dual-stimulated DOX/miRNA-34a co-delivery to tumor mass 112 , and MMP-2-triggered on-demand submission of neurotrophic growth factors (NTFs) to induce neural differentiation 113 .…”

“…DOX-encapsulated gold nanoclusters were presented for computed tomography (CT) imaging-visualized cancer chemotherapy 123 . The above MMP-2-encouraged representative achievements in cancer theranostics are summarized in Table 2 23 , 56 , 57 , 58 , 59 , 60 , 61 , 62 , 63 , 64 , 65 , 66 , 67 , 68 , 69 , 70 , 71 , 72 , 73 , 74 , 75 , 76 , 77 , 78 , 79 , 80 , 81 , 82 , 83 , 84 , 85 , 86 , 87 , 88 , 89 , 90 , 91 , 92 , 93 , 94 , 95 , 96 , 97 , 98 , 99 , 100 , 101 , 102 , 103 , 104 , 105 , 106 , 107 , 108 , 109 , 110 , 111 , 112 , 113 , 114 ...…”

Delivery of plasmid encoding interleukin-12 gene into hepatocytes by conjugated polyethylenimine-based nanoparticles

“…Nevertheless, low transfection efficiency and relatively high cytotoxicity have hampered the wide clinical application of non-viral carriers. Therefore, functionalization of non-viral delivery systems using various chemical moieties including hydrophobic chains, amino acids, carbohydrates polyethylene glycol (PEG), and targeting ligands could be considered as an effective strategy to improve the transfection efficiency and decrease the cytotoxicity (Kafshdooz et al 2016, Kim et al 2015, Malakooty Poor et al 2014, Sabahi et al 2015, Zhang et al 2016. Nanoparticle forming polymers have demonstrated great potential for the delivery of nucleic acid materials such as plasmid encoding therapeutic genes as well as siRNA, aptamers, anitisense oligonucleotides, and more recently CRISPR/CAS9 (Li et al 2015).…”

Hyaluronic acid-chitosan nanoparticles encoding CrmA attenuate interleukin-1β induced inflammation in synoviocytes in�vitro

“…Although viral gene vectors have high transfection efficiency, their poor biological safety and highly immunogenic properties restrict their application (9). By contrast, non-viral gene vectors have been widely studied due to their clinical safety (10,11).…”