State Key Laboratory of Natural Medicines, Jiangsu Key Laboratory of Drug Discovery for Metabolic Diseases, Center of Advanced Pharmaceuticals and Biomaterials, China Pharmaceutical University, Nanjing, China.
Nat Nanotechnol. 2021 Jan;16(1):104-113. doi: 10.1038/s41565-020-00793-0. Epub 2021 Jan 12.
Tumour heterogeneity remains a major challenge in cancer therapy owing to the different susceptibility of cells to chemotherapy within a solid tumour. Cancer stem-like cells (CSCs), which reside in hypoxic tumour regions, are characterized by high tumourigenicity and chemoresistance and are often responsible for tumour progression and recurrence. Here we report a nanotherapeutic strategy to kill CSCs in tumours using nanoparticles that are co-loaded with the differentiation-inducing agent, all-trans retinoic acid, and the chemotherapeutic drug, camptothecin. All-trans retinoic acid is released under hypoxic conditions, leading to CSC differentiation in the hypoxic niche. In differentiating CSC, the reactive oxygen species levels increase, which then causes the release of camptothecin and subsequent cell death. This dual strategy enables controlled drug release in CSCs and reduces stemness-related drug resistance, enhancing the chemotherapeutic response. In breast tumour mouse models, treatment with the nanoparticles suppresses tumour growth and prevents post-surgical tumour relapse and metastasis.
肿瘤异质性仍然是癌症治疗的一个主要挑战，因为实体瘤内的细胞对化疗的敏感性不同。肿瘤干细胞样细胞（CSCs）位于缺氧的肿瘤区域，其特点是高肿瘤发生和化疗耐药性，并且常常是肿瘤进展和复发的原因。在这里，我们报告了一种使用纳米颗粒的治疗策略，该纳米颗粒共同负载分化诱导剂全反式视黄酸和化疗药物喜树碱，以杀死肿瘤中的 CSCs。在缺氧条件下释放全反式视黄酸，导致缺氧龛中的 CSC 分化。在分化的 CSC 中，活性氧水平增加，随后导致喜树碱的释放和随后的细胞死亡。这种双重策略能够在 CSCs 中控制药物释放，并降低与干细胞相关的耐药性，从而增强化疗反应。在乳腺癌小鼠模型中，用纳米颗粒治疗可抑制肿瘤生长并防止术后肿瘤复发和转移。
