肺癌是第二大常见癌症，在全球癌症相关死亡中排名第一。由于对传统癌症治疗策略（包括化疗、放疗、靶向治疗和免疫疗法）产生耐药性，各种天然产物及其提取物已成为替代品。小檗碱（BBR）存在于多种树木的茎、根和树皮中，通过调节肿瘤微环境中的多种信号通路，调节肿瘤细胞增殖、凋亡、自噬、转移、血管生成和免疫反应，从而发挥抗癌活性。由于其水溶性差、药代动力学/生物利用度差以及广泛的 p-糖蛋白依赖性外排，BBR 在（预）临床研究中的应用受到限制。为了克服这些限制，BBR可以封装在基于纳米颗粒（NP）的药物递送系统中，作为单一疗法或联合疗法，并提高BBR的治疗效果。纳米制剂还有助于选择性地将 BBR 递送至肺癌细胞中。除了 BBR 的抗癌活性，特别是对肺癌的抗癌活性外，我们在此回顾了 BBR 纳米制剂在肺癌治疗中的应用，包括聚合物纳米颗粒、金属纳米颗粒、碳纳米结构等。© 2024 John Wiley

Lung cancer is the second most prevalent cancer and ranks first in cancer-related death worldwide. Due to the resistance development to conventional cancer therapy strategies, including chemotherapy, radiotherapy, targeted therapy, and immunotherapy, various natural products and their extracts have been revealed as alternatives. Berberine (BBR), which is present in the stem, root, and bark of various trees, could exert anticancer activities by regulating tumor cell proliferation, apoptosis, autophagy, metastasis, angiogenesis, and immune responses via modulating several signaling pathways within the tumor microenvironment. Due to its poor water solubility, poor pharmacokinetics/bioavailability profile, and extensive p-glycoprotein-dependent efflux, BBR application in (pre) clinical studies is restricted. To overcome these limitations, BBR can be encapsulated in nanoparticle (NP)-based drug delivery systems, as monotherapy or combinational therapy, and improve BBR therapeutic efficacy. Nanoformulations also facilitate the selective delivery of BBR into lung cancer cells. In addition to the anticancer activities of BBR, especially in lung cancer, here we reviewed the BBR nanoformulations, including polymeric NPs, metal-based NPs, carbon nanostructures, and others, in the treatment of lung cancer.© 2024 John Wiley & Sons Ltd.