A fundamental problem in oncology is that anticancer chemotherapeutics kill both cancer and healthy cells in the surrounding tissues. Resveratrol is a natural antioxidant with intriguing and opposing biological properties: it reduces viability of some cancer cells but not of non-transformed ones (in equimolar concentrations). Therefore, we examined resveratrol in human non-transformed primary astrocytes and astrocytoma. Resveratrol reduced reactive oxygen species in astrocytes, but not in astrocytoma. Such cell-type dependent response is particularly evident with analyses at the single cell level showing clear population difference in high and low glutathione levels. Due to resveratrol's poor aqueous solubility that limits its use in clinics, we incorporated it into stimulus-responsive micelles assembled from miktoarm polymers. This could be an attractive chemotherapeutic delivery strategy in nano-oncology. As a proof of principle, we show that these formulations containing resveratrol markedly decrease astrocytoma viability, particularly in combination with temozolomide, a first line chemotherapeutic for astrocytoma.

肿瘤学的一个基本问题是抗癌化疗药物会杀死周围组织中的癌细胞和健康细胞。白藜芦醇是一种天然抗氧化剂，具有有趣和相反的生物学特性：它降低了一些癌细胞的活力，但不降低非转化细胞的活力（以等摩尔浓度）。因此，我们检测了人类非转化原代星形胶质细胞和星形细胞瘤中的白藜芦醇。白藜芦醇减少了星形胶质细胞中的活性氧，但在星形细胞瘤中没有。这种依赖于细胞类型的反应在单细胞水平的分析中尤为明显，显示出高谷胱甘肽水平和低谷胱甘肽水平的明显群体差异。由于白藜芦醇的水溶性差，限制了其在临床中的使用，我们将其加入到由 miktoarm 聚合物组装而成的刺激响应胶束中。这可能是纳米肿瘤学中一种有吸引力的化学治疗递送策略。作为原理证明，我们表明这些含有白藜芦醇的制剂显着降低了星形细胞瘤的存活率，特别是与星形细胞瘤的一线化疗药物替莫唑胺联合使用。