Abstract

Metastasis remains the primary cause for mortality of breast cancer. Despite advances in current therapeutic agents, patients with metastatic breast cancer still have poor prognoses. Tumor hypoxia, a key microenvironment factor, is emerging as an attractive target to prevent metastasis and is also involved with resistance to phototherapy. Here, we show an effective nanotherapeutic approach based on manganese dioxide-coated polydopamine nanocarriers to trigger robust anti-tumor and anti-metastasis responses against metastatic breast cancer by supplemental oxygenation and multimodal imaging-guided phototherapies. In cancer cells, the produced oxygen by the developed nanoplatform decreases the expression of hypoxia-inducible factors 1\ga to inhibit tumor metastasis, and enhances the efficacy of photodynamic therapy. This nanotherapeutic approach enables the combined photodynamic/photothermal treatments with great inhibition on cell migration and invasion in vitro. Moreover, the nanotherapeutics effectively suppresses primary tumor progress and inhibits lung metastasis in vivo in a breast cancer mouse model with satisfying biosafety. This study suggests that the tumor hypoxia-targeting nanotherapeutics have great potential for preventing and treating metastatic cancers.

中文翻译：

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通过补充氧合和影像引导光疗来治疗转移性乳腺癌的有效纳米治疗方法

摘要

转移仍然是乳腺癌死亡的主要原因。尽管目前的治疗剂有所进步，但转移性乳腺癌患者的预后仍然很差。肿瘤缺氧是一种关键的微环境因素，正在成为预防转移的诱人靶标，并且还涉及对光疗的抵抗力。在这里，我们展示了一种有效的纳米治疗方法，该方法基于二氧化锰涂层的聚多巴胺纳米载体，可通过补充氧合和多模式成像引导的光疗引发针对转移性乳腺癌的强大的抗肿瘤和抗转移反应。在癌细胞中，由发达的纳米平台产生的氧气降低了缺氧诱导因子1 \ ga的表达，从而抑制了肿瘤的转移，并增强了光动力疗法的疗效。体外。此外，在具有令人满意的生物安全性的乳腺癌小鼠模型中，纳米疗法有效地抑制了原发性肿瘤的进展并在体内抑制了肺转移。这项研究表明，靶向肿瘤低氧的纳米疗法在预防和治疗转移性癌症方面具有巨大潜力。