研究动态
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自我增强的 PTX@HSA-HA 负载功能化可注射水凝胶,用于乳腺癌的有效局部化学光热治疗。

Self-enhanced PTX@HSA-HA loaded functionalized injectable hydrogel for effective local chemo-photothermal therapy in breast cancer.

发表日期:2024 Dec 01
作者: Hang Gao, Hang Li, Shuaiqiang Shao, Lintongqing Tan, Yudie Wang, Dawei Li, Wen Zhang, Tao Zhu, Guangchun Liu, Xin Meng
来源: Cell Death & Disease

摘要:

乳腺癌是严重威胁女性健康的恶性肿瘤,单一疗法无法发挥良好的肿瘤治疗效果。多种策略协同治疗可能弥补其不足,受到广泛关注。在这项研究中,巯基修饰的透明质酸(HA-SH)通过迈克尔加成反应与聚多巴胺(PDA)共价交联,开发出可注射的水凝胶,其中PDA不仅可以用作基质,还可以用作光热剂。 HSA和紫杉醇通过疏水相互作用自发组织成纳米颗粒后,低分子量的透明质酸与HSA共价连接,从而实现有效的递送。这种光热注射水凝胶包含 PTX@HSA-HA 纳米粒子,从而启动针对目标恶性肿瘤的热化疗反应。我们的结果表明,这种可注射水凝胶在小鼠乳腺癌模型中具有一致的药物输送能力,与光热疗法配合可有效抑制肿瘤生长,表现为 Ki-67 低表达和细胞凋亡增加。光热疗法(PTT)可以通过增加IL-6和TNF-α来有效刺激免疫反应。值得注意的是,该治疗没有引起任何毒性迹象。这种可注射水凝胶作为一种集光热和化疗方式于一体的多方面治疗剂具有重大前景。版权所有 © 2024 Elsevier Ltd. 保留所有权利。
Breast cancer is a malignant tumor that poses a significant threat to women's health and single therapy fails to play a good oncological therapeutic effect. Synergistic treatment with multiple strategies may make up for the deficiencies and has gained widespread attention. In this study, sulfhydryl-modified hyaluronic acid (HA-SH) was covalently crosslinked with polydopamine (PDA) via a Michael addition reaction to develop an injectable hydrogel, in which PDA can be used not only as a matrix but also as a photothermal agent. After HSA and paclitaxel were spontaneously organized into nanoparticles via hydrophobic interaction, hyaluronic acid with low molecular weight was covalently linked to HSA, thus conferring effectively delivery. This photothermal injectable hydrogel incorporates PTX@HSA-HA nanoparticles, thereby initiating a thermochemotherapeutic response to target malignancy. Our results demonstrated that this injectable hydrogel possesses consistent drug delivery capability in a murine breast cancer model, collaborating with photothermal therapy to effectively suppress tumor growth, represented by low expression of Ki-67 and increasing apoptosis. Photothermal therapy (PTT) can effectively stimulate immune response by increasing IL-6 and TNF-α. Notably, the treatment did not elicit any indications of toxicity. This injectable hydrogel holds significant promise as a multifaceted therapeutic agent that integrates photothermal and chemotherapeutic modalities.Copyright © 2024 Elsevier Ltd. All rights reserved.