Department of Orthopedics, Spinal Pain Research Institute, Shanghai Tenth People's Hospital, Tongji University School of Medicine, Shanghai 200072, P.R. China.
Biomater Sci. 2019 Nov 19;7(12):5044-5053. doi: 10.1039/c9bm00953a.
One-dimensional hydroxyapatite (HA) particularly mimics the structure of mineralized collagen fibrils and displays superior mechanical properties such as toughness. Herein, we report Se-doped HA/chitosan (Se-HA/CS) biopapers constructed with self-assembled Se-doped HA nanowires and chitosan. The Se-HA/CS biopapers with high flexibility and manufacturability can not only be further processed into arbitrary shapes by folding or using scissors but also display high performances in in vitro/vivo anti-bone tumor studies. The Se-HA/CS biopapers are more inclined to inhibit the growth of tumor cells (HCS 2/8 and SJSA cells) than that of normal human bone marrow stromal cells (hBMSCs). The potential mechanisms of this meaningful anti-tumor effect were investigated, such as reactive oxygen species accumulation and the activation of apoptosis and the underlying signal pathway involved (including caspase family, Bcl-2 family and JNK/STAT3). The results demonstrate that Se-HA/CS biopapers may inhibit the growth of HCS 2/8 and SJSA cells by synchronously inducing JNK activation and STAT3 inhibition and consequently promote the apoptosis of these cells. Furthermore, the in vivo anti-tumor studies confirm that the Se-HA/CS biopapers obviously suppress the growth of patient-derived xenograft tumor models.
一维羟基磷灰石（HA）特别模拟矿化胶原纤维的结构，并具有优异的力学性能，如韧性。在此，我们报告了用自组装的硒掺杂 HA 纳米线和壳聚糖构建的硒掺杂 HA/壳聚糖（Se-HA/CS）生物纸。具有高柔韧性和可加工性的 Se-HA/CS 生物纸不仅可以通过折叠或使用剪刀进一步加工成任意形状，而且在体外/体内抗骨肿瘤研究中也表现出优异的性能。与正常人骨髓基质细胞（hBMSCs）相比，Se-HA/CS 生物纸更倾向于抑制肿瘤细胞（HCS 2/8 和 SJSA 细胞）的生长。研究了这种有意义的抗肿瘤作用的潜在机制，如活性氧物质的积累以及细胞凋亡和涉及的潜在信号通路（包括半胱天冬酶家族、Bcl-2 家族和 JNK/STAT3）的激活。结果表明，Se-HA/CS 生物纸可能通过同步诱导 JNK 激活和 STAT3 抑制来抑制 HCS 2/8 和 SJSA 细胞的生长，从而促进这些细胞的凋亡。此外，体内抗肿瘤研究证实，Se-HA/CS 生物纸明显抑制了患者来源的异种移植肿瘤模型的生长。
