Institute of Medicinal Chemistry, Hoshi University, Ebara 2-4-41, Shinagawa-ku, Tokyo 142-8501, Japan.
Int J Pharm. 2012 Feb 28;423(2):428-34. doi: 10.1016/j.ijpharm.2011.12.015. Epub 2011 Dec 17.
Elevated interstitial fluid pressure (IFP) in a tumor is a barrier to tumor accumulation of systemic delivery of nanocarriers. In this study, we investigated whether intravenous injection of type I collagenase (collagenase-1) reduced IFP in tumors and increased the accumulation and gene expression of cationic liposome/plasmid DNA complex (lipoplex) in tumors after intravenous injection into mice bearing mouse lung carcinoma LLC tumors. Collagenase-1 reduced the amount of type I collagen in the tumor, and significantly decreased IFP by 65% at 1h after injection. Therefore, collagenase-1 induced 1.5-fold higher accumulation and 2-fold higher gene expression of lipoplex in tumors after intravenous injection. These findings indicated that intravenous injection of collagenase-1 improved the accumulation of lipoplex by decreasing IFP in tumors. These results support the potential use of collagen digestion as a strategy to improve systemic gene delivery into tumors.
肿瘤组织中升高的细胞间质液压力（IFP）是阻碍全身给药的纳米载体在肿瘤中聚集的一个障碍。在这项研究中，我们研究了静脉内注射 I 型胶原酶（胶原酶-1）是否能降低肿瘤中的 IFP，并增加静脉内注射到携带小鼠肺癌 LLC 肿瘤的小鼠后的阳离子脂质体/质粒 DNA 复合物（脂质体）在肿瘤中的积累和基因表达。胶原酶-1减少了肿瘤中 I 型胶原的量，并在注射后 1 小时使 IFP 显著降低了 65%。因此，胶原酶-1诱导脂质体在静脉内注射后在肿瘤中的积累增加了 1.5 倍，基因表达增加了 2 倍。这些发现表明，静脉内注射胶原酶-1通过降低肿瘤中的 IFP 改善了脂质体的积累。这些结果支持胶原消化作为一种改善全身基因递送到肿瘤的策略的潜力。
