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Anti-melanoma effect and action mechanism of a novel chitosan-based composite hydrogel containing hydroxyapatite nanoparticles

查看全文 作　　者：Kejia [1]Xu;Yifu [2]Wang;Yao [1]Xie;Xiaoyan [1]Zhang;Wei [1]Chen;Zhongtao [1]Li;Tingting [1]Wang;Xiao [2]Yang;Bo [3]Guo;Lin [1]Wang;Xiangdong [2]Zhu;Xingdong [2]Zhang 高影响力作者 机构地区：[1]Department of Dermatovenereology,West China Hospital,Sichuan University,Chengdu 610041,China;[2]National Engineering Research Center for Biomaterials,Sichuan University,Chengdu 610041,China;[3]Department of Ophthalmology,West China Hospital,Sichuan University,Chengdu 610041,China高影响力机构 出　　处：《Regenerative Biomaterials》索引2022年第9卷第1期,共12页高影响力期刊 基　　金：financially supported by National Key Research and Development Program of China(2017YFB0702600,2017YFB0702604);Sichuan Science and Technology Program(2020YFS0038). 摘　　要：Hydroxyapatite nanoparticles(HANPs)have been increasingly regarded and reported due to their potential anti-tumor ability.Previously,we found that the rod-like HANPs had good application potential for cutaneous melanoma(CMM).To satisfy the actual requirements in repairing post-operative skin defects and inhibiting CMM recurrence after tumorectomy,we constructed a novel chitosan/alginate(CS/Alg)hydrogel containing the aforementioned HANPs.The in vitro cell experiments confirmed that activated mitochondrial-dependent apoptosis was tightly related to the anti-tumor ability of HANPs.Specifically,we further discovered several target proteins might be involved in abnormal activating Wnt,proteoglycans in cancer,oxidative phosphorylation and p53 signaling pathways.The in vivo animal experiments demonstrated that the HANPsloaded CS/Alg hydrogel(CS/Alg/HANPs)had a similar effect on inhibiting tumor growth as HANPs,and CS/Alg hydrogel as well as phosphate buffered saline(PBS)group(control)not showed any effect,proving the key role of HANPs.The immunohistochemical staining demonstrated a tumor inhibition via the mitochondria-mediated apoptosis pathway,consistent with the in vitro evaluation.Moreover,CS/Alg/HANPs exhibited no additional biosafety risk to the functions of major organs.Overall,this CS/Alg/HANPs hydrogel has substantial application potential for treating CMM. 关 键 词：MELANOMA hydroxyapatite nanoparticles composite hydrogel tumor inhibition BIOSAFETY
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