Key Laboratory of Industrial Microbiology, Ministry of Education, College of Biotechnology, Tianjin University of Science and Technology, Tianjin 300457, China.
Shandong Academy of Pharmaceutical Sciences, Shandong Engineering Research Center of New Sustained and Controlled Release Formulations and Drug Targeted Delivery Systems, Jinan 250101, China.
Carbohydr Polym. 2024 Dec 1;345:122569. doi: 10.1016/j.carbpol.2024.122569. Epub 2024 Aug 2.
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.
乳腺癌是一种恶性肿瘤，严重威胁女性健康，单一疗法无法发挥良好的肿瘤治疗效果。采用多种策略的协同治疗可能弥补不足，并引起广泛关注。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，开发出一种可注射水凝胶，其中 PDA 不仅可用作基质，还可用作光热剂。在 HSA 和紫杉醇通过疏水相互作用自发组织成纳米颗粒后，通过共价键将低分子量透明质酸连接到 HSA 上，从而有效地进行了递药。这种光热可注射水凝胶中掺入了 PTX@HSA-HA 纳米颗粒，从而引发针对恶性肿瘤的热化疗反应。我们的研究结果表明，该可注射水凝胶在小鼠乳腺癌模型中具有一致的药物递送能力，通过光热疗法有效抑制肿瘤生长，表现为 Ki-67 表达降低和凋亡增加。光热疗法（PTT）可以通过增加 IL-6 和 TNF-α 有效刺激免疫反应。值得注意的是，该治疗没有引发任何毒性迹象。这种可注射水凝胶作为一种将光热和化疗方式相结合的多模式治疗剂具有重要的应用前景。
