Optimization of the tumor microenvironment and nanomedicine properties simultaneously to improve tumor therapy.
Optimization of the tumor microenvironment and nanomedicine properties simultaneously to improve tumor therapy.
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同时优化肿瘤微环境和纳米医学特性以改善肿瘤治疗
DOI：
10.18632/oncotarget.11546
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发表时间：
2016-09-20
期刊：
影响因子：
--
通讯作者：
Pang Z
中科院分区：
文献类型：
--
作者：
Zhang B;Shi W;Jiang T;Wang L;Mei H;Lu H;Hu Y;Pang Z
将纳米药物有效递送到肿瘤组织取决于肿瘤微环境和纳米药物性质。因此，肿瘤微环境修饰或纳米药物的先进设计正在出现，以改善纳米药物向肿瘤的递送。然而，很少有研究强调同时优化肿瘤微环境和纳米医学特性以改善肿瘤治疗的必要性。在本研究中，甲磺酸伊马替尼（IMA）用于正常化肿瘤微环境，包括血小板衍生生长因子受体-β表达抑制，肿瘤血管正常化和肿瘤灌注改善，如免疫荧光染色所示。此外，还仔细研究了肿瘤微环境正常化对不同尺寸纳米药物肿瘤递送的影响。体内荧光成像实验表明，IMA处理显着减少了110 nm左右纳米颗粒（NP）的积聚，但增强了23 nm左右胶束的积聚。此外，IMA处理限制了肿瘤内的NP的分布，但增加了胶束的分布，具有更均匀的模式。最后，抗肿瘤功效研究表明，IMA预处理可以显着增加载紫杉醇胶束的治疗效果。总之，通过同时优化纳米药物的尺寸和肿瘤微环境，为提高纳米药物向肿瘤的递送提供了一种新的策略，在临床肿瘤治疗中具有巨大的潜力。
Effective delivery of nanomedicines to tumor tissues depends on both the tumor microenvironment and nanomedicine properties. Accordingly, tumor microenvironment modification or advanced design of nanomedicine was emerging to improve nanomedicine delivery to tumors. However, few studies have emphasized the necessity to optimize the tumor microenvironment and nanomedicine properties simultaneously to improve tumor treatment. In the present study, imatinib mesylate (IMA) was used to normalize the tumor microenvironment including platelet-derived growth factor receptor-β expression inhibition, tumor vessel normalization, and tumor perfusion improvement as demonstrated by immunofluorescence staining. In addition, the effect of tumor microenvironment normalization on tumor delivery of nanomedicines with different sizes was carefully investigated. It was shown that IMA treatment significantly reduced the accumulation of nanoparticles (NPs) around 110 nm but enhanced the accumulation of micelles around 23 nm by in vivo fluorescence imaging experiment. Furthermore, IMA treatment limited the distribution of NPs inside tumors but increased that of micelles with a more homogeneous pattern. Finally, the anti-tumor efficacy study displayed that IMA pretreatment could significantly increase the therapeutic effects of paclitaxel-loaded micelles. All-together, a new strategy to improve nanomedicine delivery to tumor was provided by optimizing both nanomedicine size and the tumor microenvironment simultaneously, and it will have great potential in clinics for tumor treatment.