Release of Liposomal Contents by Cell-Secreted Matrix Metalloproteinase-9
Release of Liposomal Contents by Cell-Secreted Matrix Metalloproteinase-9
复制标题
DOI：
10.1021/bc9000646
复制
发表时间：
2009-07-01
影响因子：
4.7
通讯作者：
Mallik, Sanku
中科院分区：
文献类型：
--
作者：
Banerjee, Jayati;Hanson, Andrea J.;Mallik, Sanku
脂质体已被广泛用作药物递送载体，并且目前，超过10种脂质体制剂被食品和药物管理局批准用于临床使用。然而，在靶向时，脂质体包封的内容物的释放通常是缓慢的。我们最近已经证明，适当配制的脂质体的内容物可以通过癌症相关酶基质金属蛋白酶-9（MMP-9）快速释放。在此，我们报告了优化脂质体制剂的详细研究。通过适当地选择脂肽，主要的脂质成分，和它们的相对量，我们证明了内容物在癌症相关水平的重组人MMP-9的存在下迅速释放。我们观察到脂肽和主要脂质组分之间的脂质错配程度深刻地影响从脂质体的释放曲线。通过利用优化的脂质体制剂，我们还证明了分泌低水平MMP-9的癌细胞（HT-29）未能释放显著量的脂质体内容物。分泌高水平酶的转移性癌细胞（MCF 7）从脂质体中快速释放包封的内容物。
Liposomes have been widely used as a drug delivery vehicle, and currently, more than 10 liposomal formulations are approved by the Food and Drug Administration for clinical use. However, upon targeting, the release of the liposome-encapsulated contents is usually slow. We have recently demonstrated that contents from appropriately formulated liposomes can be rapidly released by the cancer-associated enzyme matrix metalloproteinase-9 (MMP-9). Herein, we report our detailed Studies to optimize the liposomal formulations. By properly selecting the lipopeptide, the major lipid component, and their relative amounts, we demonstrate that the contents are rapidly released in the presence of cancer-associated levels of recombinant human MMP-9. We observed that the degree of lipid mismatch between the lipopepides and the major lipid component profoundly affects the release profiles from the liposomes. By utilizing the optimized liposomal formulations, we also demonstrate that cancer cells (HT-29) which secrete low levels of MMP-9 failed to release a significant amount of the liposomal contents. Metastatic cancer cells (MCF7) secreting high levels of the enzyme rapidly release the encapsulated contents from the liposomes.