School of Basic Medicine, Qingdao University, Ningxia Road 308, Qingdao, PR China.
School of Pharmacy, Shenyang University, Wenhua Road 103, Shenyang, PR China.
Int J Pharm. 2021 Feb 1;594:120174. doi: 10.1016/j.ijpharm.2020.120174. Epub 2020 Dec 15.
Lung cancer is the leading cause of cancer death among both men and women, and non-small cell lung cancer (NSCLC) accounts for almost 80% of such death. Tumor associated macrophage (TAMs) are abundant components in NSCLC. TAMs play critical roles in angiogenesis, immune escape and chemoresistance. Here we developed a dual-targeting drug delivery system (CaZOL@BMNPs) of zoledronate, which could bind to both tumor cells with overexpressed biotin receptors and macrophage mannose receptor (MMR) positive TAMs. The biotin- and mannose-modified lipid coated calcium zoledronate nanoparticles were preferentially internalized in both tumor cells and TAMs, and thereby inhibited their survivals. Our studies demonstrated that CaZOl@BMNPs treatment obviously reduced angiogenesis, reprogrammed immunosuppressive tumor microenvironment and eventually restrained tumor progression with negligible systemic toxicity. Collectively, CaZOL@BMNPs could be a promising approach by dual-targeting tumor cells and TAMs for NSCLS chemoimmunotherapy.
肺癌是男性和女性癌症死亡的主要原因，而非小细胞肺癌（NSCLC）占此类死亡的近 80%。肿瘤相关巨噬细胞（TAMs）是 NSCLC 的丰富成分。TAMs 在血管生成、免疫逃逸和化疗耐药性方面发挥着关键作用。在这里，我们开发了一种双靶向药物递送系统（CaZOL@BMNPs）的唑来膦酸，它可以与过度表达生物素受体的肿瘤细胞和巨噬细胞甘露糖受体（MMR）阳性 TAMs 结合。生物素和甘露糖修饰的脂质包被的碳酸钙唑来膦酸纳米粒优先被肿瘤细胞和 TAMs 内化，从而抑制它们的存活。我们的研究表明，CaZOl@BMNPs 治疗明显减少了血管生成，重新编程了免疫抑制性肿瘤微环境，最终抑制了肿瘤的进展，而几乎没有全身毒性。总之，CaZOL@BMNPs 可以通过双靶向肿瘤细胞和 TAMs 为 NSCLC 化疗免疫治疗提供一种有前途的方法。
