Selenite-Releasing Bone Mineral Nanoparticles Retard Bone Tumor Growth and Improve Healthy Tissue Functions In Vivo.
Selenite-Releasing Bone Mineral Nanoparticles Retard Bone Tumor Growth and Improve Healthy Tissue Functions In Vivo.
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（封面纸）释放亚硒酸盐的骨矿物质纳米颗粒可延缓骨肿瘤生长并改善体内健康组织功能
DOI：
10.1002/adhm.201500307
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发表时间：
2015-08-26
影响因子：
10
通讯作者：
Zhang S
中科院分区：
文献类型：
--
作者：
Wang Y;Hao H;Liu H;Wang Y;Li Y;Yang G;Ma J;Mao C;Zhang S
骨肉瘤是一种原发性实体肿瘤，其中约20%来源于恶性癌性骨组织。它通常生长在长骨的干骺端，并经常转移到肺部。不幸的是，它在青少年中流行，发病率最高。尽管目前的化疗显著改善了患者的生活质量，但40-50%的患者死于肺转移。[1]经过十年的努力，骨肉瘤的治疗仍然有限。因此，研究人员转向具有抗肿瘤作用的生物材料。[2，3]理想情况下，此类生物材料不仅应填充肿瘤手术造成的骨缺损，而且应抑制肿瘤复发。因此，本工作旨在将这两种功能整合到一种生物材料中。羟基磷灰石（HA）纳米颗粒（HANs）是骨和牙釉质中的主要无机矿物。[4]近年来，通过在HA结构中掺入微量元素来修饰HA的功能引起了人们的广泛关注。各种微量元素，如镁、[5]锶、[6]硅、[7]和锌，[8]已被掺入HA晶体中，以达到刺激骨生成和抑制炎症的目的。然而，硒作为一种营养性微量元素，与关节病、心肌病、甲状腺功能、免疫功能、生殖功能等诸多健康问题密切相关，却被严重忽视。[9-11]众所周知，亚硒酸钠是硒的典型补充形式，通过其致癌诱导作用可抑制各种癌细胞的增殖。[12-14]此外，纳米材料在治疗癌症方面显示出巨大的潜力。[15-19]因此，我们提出将亚硒酸根离子掺入HA晶体可能是治疗骨肉瘤的创新思路。在此，我们首次提出研究亚硒酸根离子掺杂的HANs（HANSe）用于人骨肉瘤的体内靶向治疗。首先，建立裸鼠原位骨肉瘤模型。则
Osteosarcoma is a primary solid neoplasm, about 20% of which is derived from malignant cancerous bone tissue. It usually grows on the metaphysis of long bone, and often metastasizes to lungs. Unfortunately, it is prevalent amongst teenagers and has the highest morbidity. Although the current chemotherapy significantly improves patient’s quality of life, 40–50% of the patients die due to pulmonary metastasis.[1] After a decade’s effort, osteosarcoma was still treated with limited success. Consequently, researchers have turned to biomaterials with antitumor effects.[2, 3] Ideally, such biomaterials should not only fill the bone defects caused by the tumor surgery, but also inhibit tumor recurrence. Hence, this work aims to integrate the two functions into one biomaterial.Hydroxyapatite (HA) nanoparticles (HANs) are the main inorganic mineral in bone and tooth enamel.[4] Recently doping certain trace element into the HA structure has attracted much attention in order to modify HA functions. Various trace elements, such as magnesium,[5] strontium,[6] silicon,[7] and zinc,[8] have been incorporated into the HA crystals for the purpose of osteogenesis stimulation and inflammatory suppression. However, selenium doping has been seriously ignored although it is a nutritional trace element, which has been intimately associated with many health problems, such as arthropathy and cardiomyopathy, thyroid function, immune function and reproductive function.[9–11] It is known that sodium selenite, a typical supplementation form of selenium, can inhibit the proliferation of various kinds of cancer cells via its apoptosis-inducing effect.[12–14] In addition, nanomaterials have shown great potential in treating cancer.[15–19] Therefore, we propose that the incorporation of selenite ions into HA crystals might be an innovative idea for treating osteosarcoma. Herein, for the first time, we proposed to investigate the HANs doped with selenite ions (HANSe) for in vivo targeted treatment of osteosarcoma of human origin. Firstly, an in situ nude mouse model of osteosarcoma was constructed. Then the