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生物可吸收纳米胶束杂交水凝胶支架可预防黑色素瘤术后复发。

Bioabsorbable nano-micelle hybridized hydrogel scaffold prevents postoperative melanoma recurrence.

作者信息

Zhao Mingda, Xu Ruiling, Yang Yuedi, Tong Lei, Liang Jie, Jiang Qing, Fan Yujiang, Zhang Xingdong, Sun Yong

机构信息

National Engineering Research Center for Biomaterials, Sichuan University, 29 Wangjiang Road, Chengdu 610064, PR China; College of Biomedical Engineering, Sichuan University, 29 Wangjiang Road, Chengdu 610064, PR China.

National Engineering Research Center for Biomaterials, Sichuan University, 29 Wangjiang Road, Chengdu 610064, PR China; College of Biomedical Engineering, Sichuan University, 29 Wangjiang Road, Chengdu 610064, PR China; Sichuan Testing Centre for Biomaterials and Medical Devices, No.29 Wangjiang Road, Chengdu, Sichuan 610064, PR China.

出版信息

J Control Release. 2023 Apr;356:219-231. doi: 10.1016/j.jconrel.2023.03.005. Epub 2023 Mar 8.

Abstract

The residual and scattered small tumor tissue or cells after surgery are the main reason for tumor recurrence. Chemotherapy has a powerful ability to eradicate tumors but always accompanied by serious side effects. In this work, tissue-affinity mercapto gelatin (GelS) and dopamine-modified hyaluronic acid (HAD) were employed to fabricate a hybridized cross-linked hydrogel scaffold (HG) by multiple chemical reactions, which could integrate the doxorubicin (DOX) loaded reduction-responsive nano-micelle (PP/DOX) into this scaffold via click reaction to obtain the bioabsorbable nano-micelle hybridized hydrogel scaffold (HGMP). With the degradation of HGMP, PP/DOX was slowly released and formed targeted PP/DOX with degraded gelatin fragments as target molecules, which increased the intracellular accumulation, and inhibited the aggregation of B16F10 cells in vitro. In mouse models, HGMP absorbed the scattered B16F10 cells and released targeted PP/DOX to suppress tumorigenesis. For another, implantation of HGMP at the surgical site reduced the recurrence rate of postoperative melanoma and inhibited the growth of recurrent tumors. Meanwhile, HGMP significantly relieved the damage of free DOX to hair follicle tissue. This bioabsorbable nano-micelle hybridized hydrogel scaffold provided a valuable strategy for adjuvant therapy after tumor surgery.

摘要

手术后残留和散落的小肿瘤组织或细胞是肿瘤复发的主要原因。化疗具有强大的根除肿瘤的能力,但总是伴随着严重的副作用。在这项工作中,利用组织亲和性巯基明胶(GelS)和多巴胺修饰的透明质酸(HAD)通过多重化学反应制备了一种杂交交联水凝胶支架(HG),其可通过点击反应将负载阿霉素(DOX)的还原响应性纳米胶束(PP/DOX)整合到该支架中,从而获得可生物吸收的纳米胶束杂交水凝胶支架(HGMP)。随着HGMP的降解,PP/DOX缓慢释放,并以降解的明胶片段为靶分子形成靶向性PP/DOX,增加了细胞内积累,并在体外抑制了B16F10细胞的聚集。在小鼠模型中,HGMP吸收散落的B16F10细胞并释放靶向性PP/DOX以抑制肿瘤发生。另一方面,在手术部位植入HGMP降低了术后黑色素瘤的复发率,并抑制了复发性肿瘤的生长。同时,HGMP显著减轻了游离DOX对毛囊组织的损伤。这种可生物吸收的纳米胶束杂交水凝胶支架为肿瘤手术后的辅助治疗提供了一种有价值的策略。

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