Department of Pharmacology & Therapeutics, McGill University, Montréal, QC, Canada.
Department of Chemistry, McGill University, Montréal, QC, Canada.
Nanomedicine. 2021 Oct;37:102441. doi: 10.1016/j.nano.2021.102441. Epub 2021 Jul 22.
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.
肿瘤学中的一个基本问题是，抗癌化学疗法会杀死癌症和周围组织中的健康细胞。白藜芦醇是一种天然抗氧化剂，具有有趣且相反的生物学特性：它降低了一些癌细胞的活力，但不会降低非转化细胞的活力（在等摩尔浓度下）。因此，我们在人非转化原代星形胶质细胞和星形细胞瘤中研究了白藜芦醇。白藜芦醇降低了星形胶质细胞中的活性氧，但对星形细胞瘤没有影响。这种细胞类型依赖性反应在单细胞水平的分析中尤为明显，显示出高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较差，限制了其在临床上的应用，我们将其纳入由多臂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疗药物递送策略。作为原理的证明，我们表明这些含有白藜芦醇的制剂显著降低了星形细胞瘤的活力，特别是与替莫唑胺联合使用时，替莫唑胺是星形细胞瘤的一线化疗药物。
