Self-Assembling Imageable Silk Hydrogels for the Focal Treatment of Osteosarcoma.
Self-Assembling Imageable Silk Hydrogels for the Focal Treatment of Osteosarcoma.
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自组装可成像丝水凝胶用于骨肉瘤的局部治疗
DOI：
10.3389/fcell.2022.698282
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发表时间：
2022
影响因子：
5.5
通讯作者：
Wang, Yansong
中科院分区：
文献类型：
--
作者：
Peng, Zhibin;Li, Ming;Wang, Yuan;Yang, Hongbo;Wei, Wei;Liang, Min;Shi, Jianhui;Liu, Ruixuan;Li, Rui;Zhang, Yubo;Liu, Jingsong;Shi, Xu;Wan, Ran;Fu, Yao;Xie, Rui;Wang, Yansong
背景：骨肉瘤的标准治疗包括完全手术切除和新辅助化疗，这可能会导致严重的副作用和部分或全部失去肢体。因此，为了克服传统治疗方法的缺点，我们开发了用于骨肉瘤的自组装可成像丝素水凝胶。方法：采用CCK-8法、流式细胞术和透射电子显微镜分析碘是否诱导MG-63和Saos-2细胞凋亡。Western blotting分析碘诱导骨肉瘤细胞凋亡的途径。将聚乙二醇400、丝素溶液、聚乙烯吡咯烷酮碘(PVP-I)和泛影葡胺(MD)混合制成可成像的水凝胶。建立裸鼠骨肉瘤模型，在X线引导下将水凝胶局部注射入骨肉瘤内。对水凝胶的疗效和生物安全性进行评价。结果：18和20µM碘作用12h后，MG-63和SAO-2细胞的存活率分别下降到50±2.1%和50.5±2.7%(p<；0.01)。碘治疗组细胞凋亡率明显高于对照组(p<；0.05)，透射电子显微镜下可见明显的凋亡小体。碘可调节死亡受体途径，诱导MG-63和Saos-2细胞凋亡。这种水凝胶组装简单，在38分钟内即可形成凝胶。用注射器注射凝胶需要小于50N的力。水凝胶很容易装载，并导致持续一周以上的碘释放。聚乙二醇-碘-丝素/MD水凝胶组骨肉瘤体积明显小于其他三组(p<；0.001)。半胱氨酸天冬氨酸氨基转移酶-3和聚腺苷二磷酸核糖聚合酶(PARP)的表达水平在聚乙二醇-碘化丝/MD水凝胶组显著高于其他三组(p<；0.001)。苏木精-伊红(H&E)染色显示心、肝、脾、肺、肾、胰腺或甲状腺均未见异常。结论：自组装可成像丝素水凝胶可在X射线辅助下局部注射入骨肉瘤组织中。自组装可成像丝素水凝胶具有生物安全性好、全身毒性低、侵袭性小等优点，为改善骨肉瘤的局部控制提供了一条很有前途的途径。
Background: The standard treatment for osteosarcoma comprises complete surgical resection and neoadjuvant chemotherapy, which may cause serious side effects and partial or total limb loss. Therefore, to avoid the disadvantages of traditional treatment, we developed self-assembling imageable silk hydrogels for osteosarcoma. Methods: We analysed whether iodine induced apoptosis in MG-63 and Saos-2 cells by using CCK-8 and flow cytometry assays and transmission electron microscopy. Western blotting was used to analyse the pathway of iodine-induced apoptosis in osteosarcoma cells. PEG400, silk fibroin solution, polyvinylpyrrolidone iodine (PVP-I), and meglumine diatrizoate (MD) were mixed to produce an imageable hydrogel. A nude mouse model of osteosarcoma was established, and the hydrogel was injected locally into the interior of the osteosarcoma with X-ray guidance. The therapeutic effect and biosafety of the hydrogel were evaluated. Results: Iodine treatment at 18 and 20 µM for 12 h resulted in cell survival rate reduced to 50 ± 2.1% and 50.5 ± 2.7% for MG-63 and Sao-2 cells, respectively (p < 0.01). The proportion of apoptotic cells was significantly higher in the iodine-treatment group than in the control group (p < 0.05), and apoptotic bodies were observed by transmission electron microscopy. Iodine could regulate the death receptor pathway and induce MG-63 and Saos-2 cell apoptosis. The hydrogels were simple to assemble, and gels could be formed within 38 min. A force of less than 50 N was required to inject the gels with a syringe. The hydrogels were readily loaded and led to sustained iodine release over 1 week. The osteosarcoma volume in the PEG-iodine-silk/MD hydrogel group was significantly smaller than that in the other three groups (p < 0.001). Caspase-3 and poly (ADP-ribose) polymerase (PARP) expression levels were significantly higher in the PEG-iodine-silk/MD hydrogel group than in the other three groups (p < 0.001). Haematoxylin and eosin (H&E) staining showed no abnormalities in the heart, liver, spleen, lung, kidney, pancreas or thyroid in any group. Conclusions: Self-assembling imageable silk hydrogels could be injected locally into osteosarcoma tissues with X-ray assistance. With the advantages of good biosafety, low systemic toxicity and minimal invasiveness, self-assembling imageable silk hydrogels provide a promising approach for improving the locoregional control of osteosarcoma.
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影响因子：
5.6
作者：
Yang MH;Chung TW;Lu YS;Chen YL;Tsai WC;Jong SB;Yuan SS;Liao PC;Lin PC;Tyan YC
通讯作者：
Tyan YC
DOI：
10.1002/hed.21773
发表时间：
2012-04-01
影响因子：
2.9
作者：
Hah, J. Hun;Roh, Dong Hwan;Sung, Myung-Whun
通讯作者：
Sung, Myung-Whun
影响因子：
3.9
作者：
Basha, G;Ghirardi, M;Penninckx, F
通讯作者：
Penninckx, F
DOI：
10.1007/s10856-020-06422-5
发表时间：
2020-08-28
影响因子：
3.7
作者：
Boni, Rossana;Ali, Azam;Clarkson, Andrew N.
通讯作者：
Clarkson, Andrew N.
影响因子：
14
作者：
Hong, Heesun;Seo, Ye Been;Park, Chan Hum
通讯作者：
Park, Chan Hum