光动力疗法
肿瘤微环境
肿瘤缺氧
体内
化学
癌症研究
缺氧(环境)
细胞外基质
纳米颗粒
医学
生物物理学
透明质酸酶
材料科学
纳米技术
放射治疗
肿瘤细胞
外科
氧气
生物
生物化学
酶
有机化学
生物技术
作者
Hua Gong,Yu Chao,Jian Xiang,Xiao Han,Guosheng Song,Liangzhu Feng,Jingjing Liu,Guangbao Yang,Qian Chen,Zhuang Liu
出处
期刊:Nano Letters
[American Chemical Society]
日期:2016-03-31
卷期号:16 (4): 2512-2521
被引量:264
标识
DOI:10.1021/acs.nanolett.6b00068
摘要
Photodynamic therapy (PDT) is considered as a safe and selective way to treat a wide range of cancers as well as nononcological disorders. However, as oxygen is required in the process of PDT, the hypoxic tumor microenvironment has largely limited the efficacy of PDT to treat tumors especially those with relatively large sizes. To this end, we uncover that hyaluronidase (HAase), which breaks down hyaluronan, a major component of extracellular matrix (ECM) in tumors, would be able to enhance the efficacy of nanoparticle-based PDT for in vivo cancer treatment. It is found that the administration of HAase would lead to the increase of tumor vessel densities and effective vascular areas, resulting in increased perfusion inside the tumor. As a result, the tumor uptake of nanomicelles covalently linked with chlorine e6 (NM-Ce6) would be increased by ∼2 folds due to the improved “enhanced permeability and retention” (EPR) effect, while the tumor oxygenation level also shows a remarkable increase, effectively relieving the hypoxia state inside the tumor. Those effects taken together offer significant benefits in greatly improving the efficacy of PDT delivered by nanoparticles. Taking advantage of the effective migration of HAase from the primary tumor to its drainage sentinel lymph nodes (SLNs), we further demonstrate that this strategy would be helpful to the treatment of metastatic lymph nodes by nanoparticle-based PDT. Lastly, both enhanced EPR effect of NM-Ce6 and relieved hypoxia state of tumor are also observed after systemic injection of modified HAase, proving its potential for clinical translation. Therefore, our work presents a new concept to improve the efficacy of nanomedicine by modulating the tumor microenvironment.
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