Tumor targeting efficiency of bare nanoparticles does not mean the efficacy of loaded anticancer drugs: Importance of radionuclide imaging for optimization of highly selective tumor targeting polymeric nanoparticles with or without drug
Tumor targeting efficiency of bare nanoparticles does not mean the efficacy of loaded anticancer drugs: Importance of radionuclide imaging for optimization of highly selective tumor targeting polymeric nanoparticles with or without drug
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DOI：
10.1016/j.jconrel.2010.07.096
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发表时间：
2010-10-15
影响因子：
10.8
通讯作者：
Kim, Sang Yoon
中科院分区：
文献类型：
--
作者：
Lee, Beom Suk;Park, Kyeongsoon;Kim, Sang Yoon
更好地理解聚合物纳米颗粒作为药物递送载体是获得更有效的体内治疗反应的决定性因素。在这里，我们报告了裸聚合物纳米颗粒和载药聚合物纳米颗粒的非侵入性成像，以评估在荷瘤小鼠中的生物分布。为制备纳米级药物载体，采用不同疏水度的N-乙酰基组氨酸（NAcHis-GC-1，-2，-3）对乙二醇壳聚糖进行修饰。聚合物纳米颗粒和药物的生物分布通过使用具有I-131标记的NAcHis-GC和I-131标记的多柔比星（DOX）的γ照相机以及通过使用具有近红外荧光Cy5.5标记的NAcHis-GC的体内活动物成像来确认。在裸纳米颗粒中，NAcHis-GC 3（7.8%NAcHis含量）显示出比NAcHis-GC 1（3.3%NAcHis含量）和NAcHis-GC 2（6.8%NAcHis含量）高得多的肿瘤靶向效率。相比之下，对于载药纳米颗粒，DOX-NAcHis-GC 1显示出比DOX-NAcHis-GC 3高两倍的肿瘤靶向性质。这些数据表明裸纳米颗粒和载药纳米颗粒之间的生物分布和肿瘤靶向效率可能有很大差异。还评估了药物负载后NAcHis-GC纳米颗粒的治疗反应。在异种移植动物模型中，我们可以发现具有更高肿瘤靶向性的DOX-NAcHis-GC 1比DOX-NAcHis-GC 3和游离DOX具有更优异的治疗效果。这些结果意味着疏水核的稳定性可能是纳米颗粒肿瘤靶向效率的关键因素。本研究表明，通过使用分子成像，我们可以选择更合适的纳米粒子具有最高的肿瘤靶向性，从而发挥更出色的治疗效果在癌症治疗。(C)2010 Elsevier B. V.保留所有权利。
The better understanding of polymeric nanoparticles as a drug delivery carrier is a decisive factor to get more efficient therapeutic response in vivo. Here, we report the non-invasive imaging of bare polymeric nanoparticles and drug-loaded polymeric nanoparticles to evaluate biodistribution in tumor bearing mice. To make nano-sized drug delivery carrier, glycol chitosan was modified with different degrees of hydrophobic N-acetyl histidine (NAcHis-GC-1, -2, and -3). The biodistribution of polymeric nanoparticles and drug was confirmed by using gamma camera with I-131-labeled NAcHis-GC and I-131-labeled doxorubicin (DOX) and by using in vivo live animal imaging with near-infrared fluorescence Cy5.5-labeled NAcHis-GC. Among bare nanoparticles, NAcHis-GC3 (7.8% NAcHis content) showed much higher tumor targeting efficiency than NAcHis-GC1 (3.3% NAcHis content) and NAcHis-GC2 (6.8% NAcHis content). In contrast, for drug-loaded nanoparticles, DOX-NAcHis-GC1 displayed two-fold higher tumor targeting property than DOX-NAcHis-GC3. These data imply that the biodistribution and tumor targeting efficiency between bare and drug-loaded nanoparticles may be greatly different. Therapeutic responses for NAcHis-GC nanoparticles after drug loading were also evaluated. In xenograft animal model, we could find out that DOX-NAcHis-GC1 with higher tumor targeting of DOX has more excellent therapeutic effect than DOX-NAcHis-GC3 and free DOX. These results mean that the hydrophobic core stability might be a critical factor for tumor targeting efficiency of nanoparticles. The present study indicates that by using molecular imaging, we can select more appropriate nanoparticles with the highest tumor targeting properties, leading to exerting more excellent therapeutic results in cancer therapy. (C) 2010 Elsevier B.V. All rights reserved.