透明质酸
肿瘤微环境
细胞外基质
光动力疗法
化学
体内
癌症研究
生物物理学
癌症
癌细胞
纳米医学
光敏剂
活性氧
药物输送
医学
生物
材料科学
纳米颗粒
纳米技术
生物化学
肿瘤细胞
有机化学
生物技术
内科学
解剖
作者
Hai Yao,Kaikai Xu,Jiahong Zhou,Lin Zhou,Shaohua Wei
出处
期刊:ACS Biomaterials Science & Engineering
[American Chemical Society]
日期:2019-11-13
卷期号:6 (1): 450-462
被引量:19
标识
DOI:10.1021/acsbiomaterials.9b01544
摘要
The tumor microenvironment (TME) is composed of tumor cells, blood vessels, cancer-associated fibroblasts (CAFs), tumor extracellular matrix (ECM), et al. The TME is closely related to anticancer treatment outcome. In this manuscript, a multifunctional nanomedicine (denoted as ZDCMH NP), combining multiple TME destruction strategies into one delivery system, has been designed and fabricated. In brief, zinc phthalocyanine (ZnPc, a photosensitizer), bromopentacarbonylmanganese(I) (COMn, a CO donor), and losartan (Dup, a CAF inhibitor) were coloaded inside mesoporous silica nanoparticles (MSNs). After that, a cross-linked hyaluronic acid (HA) gel shell was encapsulated onto the surface of the MSNs to form ZDCMH NPs. After arriving at the tumor tissue, the HA gel shell could be degraded by hyaluronidase (HAase) in the ECM to trigger encapsulated drug release. After light irradiation, ZnPc generated abundant reactive oxygen species (ROS), which could provide photodynamic therapy (PDT) activity and induce COMn to release CO, which could improve the enhanced permeability and retention (EPR) effect to promote ZDCMH NP accumulation in tumor tissue. The released Dup could inhibit CAF activity and downregulate the collagen fiber concentration in the TME to promote the deep penetration of ZDCMH NPs inside solid tumors. In vitro and in vivo anticancer studies have indicated that the destruction of the TME by multiple strategies is very helpful for ZnPc to obtain satisfactory PDT efficiency.
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