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

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• 作者：Ye Zeng ; Zixuan Zhou ; Minmin Fan ; Tao GongZhirong Zhang ; Xun Sun
• 刊名：Molecular Pharmaceutics
• 出版年：2017
• 出版时间：January 3, 2017
• 年：2017
• 卷：14
• 期：1
• 页码：81-92
• 全文大小：743K
• ISSN：1543-8392

文摘

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