阿霉素
材料科学
细胞外基质
胶原酶
肿瘤微环境
体内
生物物理学
癌症研究
纳米笼
纳米颗粒
胶囊
化学
生物化学
酶
纳米技术
化疗
医学
生物
肿瘤细胞
催化作用
生物技术
外科
植物
作者
Hanchun Yao,Xin Guo,Huijuan Zhou,Jianzhuang Ren,Ying Liu,Songchao Duan,Xiaobao Gong,Bin Du
标识
DOI:10.1021/acsami.0c03022
摘要
Dense extracellular matrix (ECM) severely impedes the spread of drugs in solid tumors and induces hypoxia, reducing chemotherapy efficiency. Different proteolytic enzymes, such as collagenase (Col) or bromelain, can directly attach to the surface of nanoparticles and improve their diffusion, but the method of ligation may also impair the enzymatic activity due to conformational changes or blockage of the active site. Herein, a “nanoenzyme capsule” was constructed by combining collagenase nanocapsules (Col-nc) with heavy-chain ferritin (HFn) nanocages encapsulating the chemotherapy drug doxorubicin (DOX) to enhance tumor penetration of the nanoparticles by hydrolyzing collagen from the ECM. Col-nc could protect the activity of the enzyme before reaching the site of action while being degraded under mildly acidic conditions in tumors, and the released proteolytic enzyme could digest collagen. In addition, HFn as a carrier could effectively load DOX and had a self-targeting ability, enabling the nanoparticles to internalize into cancer cells more effectively. From in vivo and in vitro studies, we found that collagen was effectively degraded by Col-nc/HFn(DOX) to increase the accumulation and penetration of nanoparticles in the solid tumor site and could alleviate hypoxia inside the tumor to enhance the antitumor effects of DOX. Therefore, the strategy of increasing nanoparticle penetration in this system is expected to provide a potential approach for the clinical treatment of solid tumors.
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