A novel method for Imaging in vivo degradation of poly(L-glutamic acid), a biodegradable drug carrier
A novel method for Imaging in vivo degradation of poly(L-glutamic acid), a biodegradable drug carrier
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DOI：
10.1007/s11095-007-9253-0
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发表时间：
2007-06-01
影响因子：
3.7
通讯作者：
Li, Chun
中科院分区：
文献类型：
--
作者：
Melancon, Marites P.;Wang, Wei;Li, Chun
目的.开发一种基于L-PG的成像探针，适用于评估L-PG在体内的降解。L-PG和近红外荧光（NIRF）染料NIR 813的缀合物的特征在于关于猝灭效率和通过组织蛋白酶B（CB）和其他蛋白酶的降解性。采用NIRF光学成像技术（n = 3）评价L-PG-NIR 813的降解动力学及其在裸鼠原位人U87/TGL胶质瘤中静脉注射后的降解。来自L-PG-NIR 813的荧光信号在8- 10%的NIR 813负载下被有效地猝灭和活化。暴露于CB后，L-PG-NIR 813的荧光强度增加10倍。L-PG-NIR 813也被另一种半胱氨酸蛋白酶组织蛋白酶L降解，但不被MMP-2、组织蛋白酶E、组织蛋白酶D和纤溶酶降解。选择性CB抑制剂阻断荧光激活。静脉注射后，L-PG-NIR 813的降解主要在肝脏中可见，在注射后4 h达到峰值。在U87/TGL肿瘤中，L-PG-NIR 813被激活，而D-PG-NIR 813未被激活。我们的研究结果表明，L-PG-NIR 813可用于监测L-PG为基础的聚合物药物的体内降解，并且该试剂可证明可用于蛋白酶活性的非侵入性成像，特别是半胱氨酸蛋白酶。
Purpose. To develop an L-PG-based imaging probe suitable for assessing the degradation of L-PG in vivo.Materials and Methods. Conjugates of L-PG and a near-infrared fluorescence (NIRF) dye, NIR813, were characterized with regard to quenching efficiency and degradability by cathepsin B (CB) and other proteases. The kinetics of L-PG-NIR813's degradation and its degradation in orthotopic human U87/TGL glioma in nude mice after intravenous injection was assessed using NIRF optical imaging (n = 3).Results. The fluorescence signal from L-PG-NIR813 was efficiently quenched and activated at NIR813 loadings of 8-10%. Upon exposure to CB, the fluorescence intensity of L-PG-NIR813 increased 10-fold. L-PG-NIR813 was also degraded by another cysteine protease cathepsin L, but not by MMP-2, cathepsin E, cathepsin D, and plasmin. A selective CB inhibitor blocked the fluorescence activation. After intravenous injection, the degradation of L-PG-NIR813 was visualized primarily in the liver, which peaked at 4 h postinjection. Activation of L-PG-NIR813 but not D-PG-NIR813 was clearly seen in U87/TGL tumors.Conclusion. Our results indicate that L-PG-NIR813 may be used to monitor the in vivo degradation of L-PG-based polymeric drugs, and that this agent may prove useful in noninvasive imaging of protease activity, particularly that of cysteine proteases.