Lanthanum-Doped Chitosan Hydrogels Promote the Apoptosis of Melanoma Cells by Bcl-2/Bax Pathway.
Lanthanum-Doped Chitosan Hydrogels Promote the Apoptosis of Melanoma Cells by Bcl-2/Bax Pathway.
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DOI：
10.1021/acsabm.8b00417
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发表时间：
2018-10
影响因子：
4.7
通讯作者：
Jiawei Lu;Yu Miao;Cui‐Xiang Guo;Qinfei Ke;J. Yin;Shumin Zhou;Yaping Guo
中科院分区：
文献类型：
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作者：
Jiawei Lu;Yu Miao;Cui‐Xiang Guo;Qinfei Ke;J. Yin;Shumin Zhou;Yaping Guo
黑色素瘤的手术切除可能会造成皮肤伤口，而残留的黑色素瘤细胞带来肿瘤复发的巨大风险。为了克服上述问题，我们首次构建了具有优异伤口愈合和抗肿瘤功能的掺镧壳聚糖（La-CS）水凝胶。 La元素均匀分散在整个水凝胶中，部分La3+离子与CS反应形成La-CS络合物。 La3+离子与CS之间的络合相互作用显着提高了La-CS水凝胶的La3+释放性能。复合水凝胶释放的La3+离子选择性抑制B-16黑色素瘤细胞的增殖，但对L929皮肤成纤维细胞的毒副作用较低。此外，La3+离子通过Bcl-2/Bax途径引发B-16细胞凋亡，Annexin Vand PI双染、流式细胞术和Western blot结果证实。 C57小鼠体内肿瘤模型显示，La-CS水凝胶比纯CS水凝胶对B-16黑色素瘤细胞具有更显着的复发抑制作用。同时，多功能水凝胶加速了体内伤口愈合。这一令人兴奋的发现为构建用于肿瘤治疗的La掺杂水凝胶提供了一种关键且有前景的策略。
The surgical resection of melanoma may cause skin wounds, and the remaining melanoma cells bring a great risk of tumor recurrence. To overcome the above problem, we for the first time constructed lanthanum-doped chitosan (La-CS) hydrogels with excellent wound healing and antitumor functions. The La element was uniformly dispersed within whole hydrogels, and part of La3+ ions reacted with CS to form La-CS complex. The complexation interaction between La3+ ions and CS significantly improve the La3+ release performances of La-CS hydrogels. The as-released La3+ ions from the composite hydrogels selectively inhibited the proliferation of B-16 melanoma cells, but showed lower toxic side effects to L929 skin fibroblast cells. Moreover, the La3+ ions triggered the apoptosis of B-16 cells through Bcl-2/Bax pathway, as confirmed by the Annexin Vand PI double staining, flow cytometry, and Western blot results. The in vivo tumor models of C57 mice revealed that the La-CS hydrogels had more significant relapse-inhibition effects on B-16 melanoma cells than the pure CS hydrogels. At the same time, the in vivo wound healing was accelerated by the multifunctional hydrogels. The exciting finding provides a critical and promising strategy in the construction of La-doped hydrogels for oncotherapy.