锶掺杂羟基磷灰石纳米复合材料通过调节骨形成和抑制癌细胞干性治疗乳腺癌骨转移

IF 2.6 4区 材料科学 Q3 CHEMISTRY, MULTIDISCIPLINARY
Yanlian Lu, Zhengjie Liu, Mengmeng Ji, Lili Ren, Yanru Song, Guoqiang Zhou, Hua Yang, Kun Ge
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引用次数: 0

摘要

骨转移是晚期乳腺癌患者最常见的发病率。在临床上,化疗药物和抗骨吸收药物被用来抑制癌细胞和破骨细胞的活性,以降低骨相关事件的发生率。然而,乳腺癌骨转移患者的无进展生存率和5年生存率仍然很低。一旦发生骨转移,肿瘤细胞破坏骨微环境的平衡,引起溶骨病变,增强肿瘤细胞的干性,加速转移。因此,针对骨微环境的复杂性,本研究开发了新型靶向治疗乳腺癌骨转移的20%Sr/HAP@CS@miR34a纳米复合材料。采用水热法制备了20%掺锶羟基磷灰石纳米颗粒(20%Sr/HAP),该纳米颗粒具有促进成骨分化和抑制破骨细胞分化的能力。通过修饰壳聚糖,负载miR34a,构建了20%Sr/HAP@CS@miR34a纳米复合材料。20%Sr/HAP@CS静脉注射后小鼠显示出安全的骨靶向能力。20%Sr/HAP@CS@miR34a可减弱乳腺癌细胞的干性,减少浸润和转移。20%Sr/HAP@CS@miR34a在体外也能抑制破骨细胞样细胞的形成,并在乳腺癌骨转移的3D共培养模型中缓解骨溶解。因此,20%Sr/HAP@CS@miR34a纳米复合材料在骨微环境中为乳腺癌骨转移提供了一种骨靶向治疗策略。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
Strontium-doped hydroxyapatite nanocomposites for breast cancer bone metastasis therapy by modulating bone formation and suppressing cancer cell stemness

Bone metastases is the most common incidence in the advanced stage of breast cancer patients. In clinic, chemotherapeutic drugs and anti-resorptive drugs are used to suppress cancer cell and osteoclast activity for the decreased incidence of bone-related events. However, the progression-free and 5-year survival rate is still very low in patients with breast cancer bone metastasis. Once bone metastasis occurs, tumor cells disrupt the bone microenvironment’s balance, causing osteolytic lesions and strengthening tumor cell stemness to accelerate metastasis. Therefore, addressing the complexity of bone microenvironment, this work developed new targeted therapeutic nanocomposites 20%Sr/HAP@CS@miR34a for breast cancer bone metastasis. The twenty-percentage strontium-doped hydroxyapatite nanoparticles (20%Sr/HAP) were prepared by hydrothermal method and had the ability to promote osteogenic differentiation and inhibit osteoclast differentiation. The nanocomposites 20%Sr/HAP@CS@miR34a was constructed by modifying chitosan and loading miR34a. 20%Sr/HAP@CS showed safe and bone-targeting capacity in mice after intravenous injection. 20%Sr/HAP@CS@miR34a weakened the stemness of breast cancer cells and decreased invasion and metastasis. 20%Sr/HAP@CS@miR34a also suppressed the formation of osteoclast-like cells in vitro and alleviated osteolysis in the 3D co-culture model of breast cancer bone metastasis. Therefore, 20%Sr/HAP@CS@miR34a nanocomposites provide a bone-targeting therapeutic strategy in the bone microenvironment for breast cancer bone metastasis.

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来源期刊
Journal of Nanoparticle Research
Journal of Nanoparticle Research 工程技术-材料科学:综合
CiteScore
4.40
自引率
4.00%
发文量
198
审稿时长
3.9 months
期刊介绍: The objective of the Journal of Nanoparticle Research is to disseminate knowledge of the physical, chemical and biological phenomena and processes in structures that have at least one lengthscale ranging from molecular to approximately 100 nm (or submicron in some situations), and exhibit improved and novel properties that are a direct result of their small size. Nanoparticle research is a key component of nanoscience, nanoengineering and nanotechnology. The focus of the Journal is on the specific concepts, properties, phenomena, and processes related to particles, tubes, layers, macromolecules, clusters and other finite structures of the nanoscale size range. Synthesis, assembly, transport, reactivity, and stability of such structures are considered. Development of in-situ and ex-situ instrumentation for characterization of nanoparticles and their interfaces should be based on new principles for probing properties and phenomena not well understood at the nanometer scale. Modeling and simulation may include atom-based quantum mechanics; molecular dynamics; single-particle, multi-body and continuum based models; fractals; other methods suitable for modeling particle synthesis, assembling and interaction processes. Realization and application of systems, structures and devices with novel functions obtained via precursor nanoparticles is emphasized. Approaches may include gas-, liquid-, solid-, and vacuum-based processes, size reduction, chemical- and bio-self assembly. Contributions include utilization of nanoparticle systems for enhancing a phenomenon or process and particle assembling into hierarchical structures, as well as formulation and the administration of drugs. Synergistic approaches originating from different disciplines and technologies, and interaction between the research providers and users in this field, are encouraged.
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