Matrix metalloprotease 2-responsive multifunctional liposomal nanocarrier for enhanced tumor targeting.
Matrix metalloprotease 2-responsive multifunctional liposomal nanocarrier for enhanced tumor targeting.
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DOI：
10.1021/nn300524f
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发表时间：
2012-04-24
期刊：
影响因子：
17.1
通讯作者：
Torchilin VP
中科院分区：
文献类型：
--
作者：
Zhu L;Kate P;Torchilin VP
为了响应肿瘤微环境中上调的基质金属蛋白酶2(MMP2)的表达，并改善负载药物的癌细胞特异性递送，成功开发了一种新型的智能多功能给药系统。该体系是一种表面功能化的脂质体纳米载体，合成并表征了两种功能性聚乙二醇脂联物。用肿瘤细胞特异性抗核小体单抗(MAb2C5)进一步修饰功能化脂质体。在最终的系统中，几种药物输送策略以一种简单的方式组合在同一个纳米载体中，并以最佳方式进行协调。纳米载体的功能包括：i)亲水且灵活的长的聚乙二醇链，以防止纳米载体的非特异性相互作用并延长其循环时间；ii)纳米尺度的系统，允许其通过增强的渗透性和滞留(EPR)效应进行被动的肿瘤靶向；iii)mAb2C5，以允许特异性靶向肿瘤细胞；iv)在聚乙二醇和脂类之间的基质金属蛋白酶2敏感的键，其在肿瘤中通过高表达的细胞外MMP2裂解以去除聚乙二醇链；V)细胞穿透肽(TATP)在去除长链聚乙二醇并暴露先前隐藏的表面附着的TATP后，触发系统的增强细胞内递送。结果表明，这种设计可以增强纳米载体在癌细胞中的靶向性和内在化。
A novel “smart” multifunctional drug delivery system was successfully developed to respond to the up-regulated matrix metalloprotease 2 (MMP2) in the tumor microenvironment and improve cancer cell-specific delivery of loaded drugs. The system represents a surface-functionalized liposomal nanocarrier, for which two functional polyethylene glycol (PEG)-lipid conjugates were synthesized and characterized. The functionalized liposome was further modified with the tumor cell-specific anti-nucleosome monoclonal antibody (mAb 2C5). In the resulting system, several drug delivery strategies were combined in the same nanocarrier in a simple way and coordinated in an optimal fashion. The functions of the nanocarrier include: i) the hydrophilic and flexible long PEG chains to prevent nanocarrier non-specific interactions and prolong its circulation time; ii) a nanoscale size of the system that allows for its passive tumor targeting via the enhanced permeability and retention (EPR) effect; iii) a mAb 2C5 to allow for the specific targeting of tumor cells; iv) a matrix metalloprotease 2-sensitive bond between PEG and lipid that undergoes cleavage in the tumor by the highly expressed extracellular MMP2 for the removal of PEG chains; v) The cell-penetrating peptide (TATp) triggering of the enhanced intracellular delivery of the system after long-chain PEG removal and exposure of the previously hidden surface-attached TATp. It is shown that such a design can enhance the targetability and internalization of nanocarriers in cancer cells.
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影响因子：
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