Enzyme-triggered size shrink and laser-enhanced NO release nanoparticles for deep tumor penetration and combination therapy
Enzyme-triggered size shrink and laser-enhanced NO release nanoparticles for deep tumor penetration and combination therapy
复制标题
酶触发尺寸缩小和激光增强 NO 释放纳米颗粒，用于肿瘤深层渗透和联合治疗
DOI：
10.1016/j.biomaterials.2018.03.046
复制
发表时间：
2018-06-01
期刊：
影响因子：
14
通讯作者：
Gao, Huile
中科院分区：
文献类型：
--
作者：
Hu, Chuan;Cun, Xingli;Gao, Huile
由于肿瘤的异质性，化疗仍受到药物递送效果差的限制。在此，我们提出了一种新的纳米颗粒，它不仅可以响应肿瘤微环境，而且可以调节它，用于深入肿瘤渗透和联合治疗。以透明质酸酶（HAase）引发的透明质酸收缩壳层为载体，分别以近红外激光敏感的一氧化氮供体（HN）、阿霉素（DOX）的小分子树枝状前体药物（IDD）和吲哚菁绿色（ICG）为光热剂，将透明质酸收缩壳层修饰成智能纳米粒（IDDHN）。IDDHN在体外和体内均表现出协同的深度渗透，这是由于HAase介导的酶促降解HN壳和激光增强的NO释放触发ICG在NIR激光照射下的强烈热效应的深度渗透。在4T1异种移植瘤模型中验证了IDDHN的治疗效果，并且在NIR激光照射下显示出更好的抗肿瘤效果，并且副作用很少。因此，本研究的有效性可能为设计纳米粒子提供一种新的策略，既能响应肿瘤微环境又能调节肿瘤微环境，从而改善治疗药物在肿瘤中的渗透性和异质性分布。(C)2018爱思唯尔有限公司版权所有。
Chemotherapy remains restricted by poor drug delivery efficacy due to the heterogenous nature of tumor. Herein, we presented a novel nanoparticle that could not only response to the tumor microenvironment but also modulate it for deep tumor penetration and combination therapy. The intelligent nanoparticle (IDDHN) was engineered by hyaluronidase (HAase)-triggered size shrinkable hyaluronic acid shells, which were modified with NIR laser sensitive nitric oxide donor (HN), small-sized dendrimeric prodrug (IDD) of doxorubicin (DOX) as chemotherapy agent and indocyanine green (ICG) as photothermal agent into a single nanoparticle. IDDHN displayed synergistic deep penetration both in vitro and in vivo, owing to the enzymatically degradable HN shell mediated by HAase and laser enhanced NO release triggered deep penetration upon strong hyperthermia effect of ICG under the NIR laser irradiation. The therapeutic effect of IDDHN was verified in 4T1 xenograft tumor model, and IDDHN showed a much better antitumor efficiency with few side effects upon NIR laser irradiation. Therefore, the valid of this study might provide a novel tactic for engineering nanoparticles both response to and modulate the tumor microenvironment for improving penetration and heterogeneity distribution of therapeutic agents in tumor. (C) 2018 Elsevier Ltd. All rights reserved.