PEGylated Cationic Vectors Containing a Protease-Sensitive Peptide as a miRNA Delivery System for Treating Breast Cancer

• DOI: 10.1021/acs.molpharmaceut.6b00726
• Publication Date: 2016-11-27T21:47:53Z
• Authors: Ye Zeng; Zixuan Zhou; Minmin Fan; Tao Gong; Zhirong Zhang; Xun Sun
• Keywords: Polyethylenimine

Several targeted drug delivery systems have recently been developed to increase the bioavailability of a at its site action, allowing simultaneous reduction total necessary dose as well side effects. Here, we designed cationic gene vector containing matrix metalloproteinase-2 (MMP2)-cleavable substrate peptides that specifically target tumor sites where MMP2 levels are high. The system is fabricated by linking enzyme-cleavable polyethylene glycol (PEG) derivatives β-cyclodextrin-polyethylenimine conjugates, which reduce toxicity polyethylenimine and condense therapeutic cargo. In present study, suppressor microRNA miR-34a, suppresses onset progression many types cancers, was investigated for potential treating breast cancer. PEG coating markedly reduces nonspecific interaction between particles serum proteins, permitting accumulation site; subsequent peptide cleavage facilitates miR-34a into cells. nanopreparation shows excellent stability, internalization, targeting, antitumor efficacy in vitro vivo better than those MMP2-uncleavable peptide.