Shanghai Key Laboratory of Regulatory Biology, School of Life Sciences, East China Normal University, Shanghai, 200241, PR China.
Shanghai Key Laboratory of Regulatory Biology, School of Life Sciences, East China Normal University, Shanghai, 200241, PR China.
Biomaterials. 2019 May;203:63-72. doi: 10.1016/j.biomaterials.2019.02.023. Epub 2019 Mar 1.
Photothermal therapy efficiently ablates tumors via hyperthermia but inevitably induces serious side effects including thermal damage to normal tissues, inflammations and enhanced risk of tumor metastasis. In this study, we fabricated a dual peptide decorated melanin-like nanoparticle for tumor-targeted and autophagy-promoted photothermal therapy in pursuit of improved cancer treatment. The multifunctional nanoparticle was composed of dual peptide RGD- and beclin 1-modified and PEGylated melanin-like polydopamine nanoparticles. Beclin 1-derived peptide modified on the nanoparticle up-regulated autophagy in cancer cells and further sensitized the tumors to photothermal ablation. RGD decorated on the particle surface enhanced the selectivity and cellular uptake of polydopamine nanoparticles by breast cancer cells. In vivo therapeutic experiments revealed that the tumor-targeted and autophagy promotion-associated photothermal therapy efficiently regressed tumors at a low temperature around 43 °C. The study provides a novel and efficient strategy to improve the efficiency of photothermal therapy via the up-regulation of autophagy in tumor cells.
光热疗法通过高热有效地消融肿瘤，但不可避免地会引起严重的副作用，包括对正常组织的热损伤、炎症和增加肿瘤转移的风险。在这项研究中，我们制备了一种双肽修饰的黑色素样纳米颗粒，用于肿瘤靶向和自噬促进的光热治疗，以寻求改善癌症治疗的方法。该多功能纳米颗粒由双肽 RGD 和自噬相关蛋白 1（beclin 1）修饰的聚多巴胺纳米颗粒组成。修饰在纳米颗粒上的 beclin 1 衍生肽在上皮性乳腺癌细胞中上调自噬，进一步使肿瘤对光热消融敏感。颗粒表面修饰的 RGD 增强了多聚多巴胺纳米颗粒对乳腺癌细胞的选择性和细胞摄取。体内治疗实验表明，靶向肿瘤和促进自噬相关的光热治疗在 43°C 左右的低温下能有效地消退肿瘤。该研究为通过上调肿瘤细胞自噬来提高光热治疗的效率提供了一种新的、有效的策略。
