Department of Material Sciences and Engineering, University of Washington, Seattle, WA, 98195, USA.
Department of Neurological Surgery, University of Washington, Seattle, WA, 98195, USA.
Adv Healthc Mater. 2019 Oct;8(20):e1900826. doi: 10.1002/adhm.201900826. Epub 2019 Sep 26.
Intratumoral hypoxia is a major contributor to multiple drug resistance (MDR) in cancer, and can lead to poor prognosis of patients receiving chemotherapy. Development of an MDR-inhibitor that mitigates the hypoxic environment is crucial for cancer management and treatment. Reported is a biocompatible and biodegradable catalase-conjugated iron oxide nanoparticle (Cat-IONP) capable of converting reactive oxygen species to molecular oxygen to supply an oxygen source for the hypoxic tumor microenvironment. Cat-IONP demonstrates initial enzymatic activity comparable to free catalase while providing a nearly threefold increase in long-term enzymatic activity. It is demonstrated that Cat-IONP significantly reduces the in vitro expression of hypoxia-inducible factors at the transcription level in a breast cancer cell line. Co-treatment of Cat-IONP and paclitaxel (PTX) significantly increases the drug sensitivity of hypoxic-cultured cells, demonstrating greater than twofold and fivefold reduction in cell viability in comparison to cells treated only with 80 and 120 × 10 m PTX, respectively. These findings demonstrate the ability of Cat-IONP to act as an MDR-inhibitor at different biological levels, suggesting a promising strategy to combat cancer-MDR and to optimize cancer management and treatment outcomes.
肿瘤内缺氧是癌症多药耐药（MDR）的主要原因之一，可导致接受化疗的患者预后不良。开发一种能够减轻缺氧环境的 MDR 抑制剂对于癌症的管理和治疗至关重要。本文报道了一种具有生物相容性和可生物降解性的过氧化氢酶偶联氧化铁纳米颗粒（Cat-IONP），它能够将活性氧转化为分子氧，为缺氧肿瘤微环境提供氧气源。Cat-IONP 表现出与游离过氧化氢酶相当的初始酶活性，同时将长期酶活性提高近三倍。研究表明，Cat-IONP 可显著降低乳腺癌细胞系中转录水平缺氧诱导因子的表达。Cat-IONP 与紫杉醇（PTX）联合治疗可显著提高缺氧培养细胞的药物敏感性，与仅用 80 和 120×10 m PTX 处理的细胞相比，细胞活力分别降低了两倍和五倍以上。这些发现表明 Cat-IONP 能够在不同的生物学水平上作为 MDR 抑制剂发挥作用，为克服癌症-MDR 和优化癌症管理和治疗结果提供了一种有前途的策略。
