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基于壳聚糖的具有止血和抗菌活性的热敏可注射水凝胶,通过化学光热疗法预防乳腺癌术后复发和转移。

Chitosan-based thermosensitive injectable hydrogel with hemostatic and antibacterial activity for preventing breast cancer postoperative recurrence and metastasis via chemo-photothermal therapy.

作者信息

Hou Xueyan, Guan Yalin, Lu Yanan, Wang Yuxin, Xu Suyue, Zhu Huiqing, Zhao Jingya, Xiao Liu, He Sisi, Shi Yongli

机构信息

College of pharmacy, Xinxiang Medical University, 453003 Xinxiang, PR China; Pingyuan Laboratory, 453007 Xinxiang, PR China.

College of pharmacy, Xinxiang Medical University, 453003 Xinxiang, PR China.

出版信息

Int J Biol Macromol. 2025 Feb;290:138930. doi: 10.1016/j.ijbiomac.2024.138930. Epub 2024 Dec 17.

Abstract

Primary resection surgery is a conventional approach in breast cancer treatment, which plays a pivotal role in the prevention of recurrence and metastasis. In this study, an injectable hydrogel comprising chitosan (CS), β-glycerophosphate (β-GP), and dopamine (DA) with near-infrared (NIR) photothermal attributes was developed. The composite hydrogels integrate doxorubicin (DOX), termed DCGD, and can be used for chemotherapy, synergistic photothermal therapy, anti-bacterial and hemostasis. Local administration of injectable DCGD hydrogels into breast cancer resection cavities could prevent the postoperative breast cancer recurrence and metastasis via chemo-photothermal therapy. Additionally, the remarkable hemostatic and anti-bacterial properties of DCGD facilitated postoperative wound healing. Notably, the DCGD hydrogel had a dual pH- and photothermal-responsive DOX release profile, ensuring sustained drug release to residual tumor tissues triggered by NIR laser irradiation and the acidic tumor microenvironment. Histological analyses including H&E, TUNEL, and Ki67 immunohistochemistry confirmed the potent anti-recurrent and anti-metastatic efficacy of DCGD hydrogels. Therefore, the DCDG hydrogels developed in our study had the favorable hemostatic, anti-bacterial, photothermal and drug-loading effects, which provided a new strategy for postoperative breast cancer recurrence and metastasis treatment.

摘要

原发性切除手术是乳腺癌治疗中的一种传统方法,在预防复发和转移方面起着关键作用。在本研究中,开发了一种由壳聚糖(CS)、β-甘油磷酸酯(β-GP)和具有近红外(NIR)光热特性的多巴胺(DA)组成的可注射水凝胶。这种复合水凝胶整合了阿霉素(DOX),称为DCGD,可用于化疗、协同光热疗法、抗菌和止血。将可注射的DCGD水凝胶局部注射到乳腺癌切除腔内,可通过化学光热疗法预防术后乳腺癌的复发和转移。此外,DCGD显著的止血和抗菌特性促进了术后伤口愈合。值得注意的是,DCGD水凝胶具有双pH和光热响应的DOX释放曲线,确保由近红外激光照射和酸性肿瘤微环境触发的药物持续释放到残留肿瘤组织中。包括苏木精-伊红染色(H&E)、末端脱氧核苷酸转移酶介导的缺口末端标记法(TUNEL)和Ki67免疫组织化学在内的组织学分析证实了DCGD水凝胶强大的抗复发和抗转移功效。因此,我们研究中开发的DCDG水凝胶具有良好的止血、抗菌、光热和载药效果,为术后乳腺癌复发和转移的治疗提供了一种新策略。

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