Hierarchically constructed selenium-doped bone-mimetic nanoparticles promote ROS-mediated autophagy and apoptosis for bone tumor inhibition
Hierarchically constructed selenium-doped bone-mimetic nanoparticles promote ROS-mediated autophagy and apoptosis for bone tumor inhibition
复制标题
分层构建的硒掺杂仿骨纳米粒子促进ROS介导的自噬和细胞凋亡，从而抑制骨肿瘤
DOI：
10.1016/j.biomaterials.2020.120253
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发表时间：
2020-10-01
期刊：
影响因子：
14
通讯作者：
Zhang, Shengmin
中科院分区：
文献类型：
--
作者：
Li, Xiao;Wang, Yifan;Zhang, Shengmin
由于仿生材料与自然组织高度相似，通常能够潜移默化地影响组织的发育、再生和致癌。尽管在组织工程中使用这类材料有好处，但它们在癌症治疗中的潜在应用一直被忽视，特别是仿生材料介导肿瘤抑制的功能和机制。在这里，我们制备了模拟骨结构的掺硒羟基磷灰石纳米颗粒(B-SeHANs)，它概括了骨HA的单轴取向的分层结构，通过硒的化疗和羟基磷灰石促进骨修复，在骨肿瘤的术后治疗中具有潜在的双重作用，系统地研究了类骨分层结构在SeHANs体内和体外抑制骨肿瘤中的影响。我们发现，与非仿生SeHAN相比，B-SeHAN表现出高度的细胞内化和细胞内降解，并通过ROS介导的JNK途径的激活和Akt/mTOR途径的抑制，诱导随后的自噬和caspase依赖的细胞凋亡。我们进一步证实，在设计良好的原位胫骨肿瘤模型中，B-SeHAN促进自噬和凋亡以抑制肿瘤生长，同时显著减少骨破坏。本工作为仿生矿物纳米颗粒抑制肿瘤生长的开发、评价和基础研究提供了可行的策略。
Biomimetic materials are often capable of subtly affecting tissue development, regeneration and carcinogenesis due to their high similarity to natural tissues. Despite the benefit of using such materials in tissue engineering, their prospective use in cancer therapy has been neglected, particularly the functions and mechanisms by which biomimetic materials mediate tumor suppression. Here, we prepare hierarchically constructed bone-mimetic selenium-doped hydroxyapatite nanoparticles (B-SeHANs), which recapitulate the uniaxially oriented hierarchical structure of bone HA and can potentially play a dual role in the postoperative treatment of bone tumors via the chemotherapy from selenium and the promotion of bone repair by hydroxyapatite, to systematically investigate the influence of bone-mimetic hierarchical structure in bone tumor inhibition by SeHANs in vivo and in vitro. We found that, compared to the non-biomimetic SeHANs, the B-SeHANs exhibited highly enhanced cellular internalization and intracellular degradation, and induced subsequent autophagy and caspase-dependent apoptosis via the ROS-mediated activation of the JNK pathway and inhibition of the Akt/mTOR pathway. We further verified that the B-SeHANs promoted autophagy and apoptosis to inhibit tumor growth while profoundly reducing bone destruction in a well-designed orthotopic tibial tumor model. The current work presents a feasible strategy for the development, evaluation and fundamental study of biomimetic mineral nanoparticles to inhibit tumor growth.