Xiang Ling, Fang Changlong, Feng Jiaxing, Tan Yulu, Wu Qingsi, Zhou Xueru, Li Jia, Gong Tao
Key Laboratory of Drug-Targeting and Drug Delivery System of the Education Ministry and Sichuan Province, Sichuan Engineering Laboratory for Plant-Sourced Drug and Sichuan Research Center for Drug Precision Industrial Technology, West China School of Pharmacy, Sichuan University, Chengdu 610041, China.
West China Hospital of Stomatology, Sichuan University, Chengdu 610041, China.
Eur J Pharm Biopharm. 2023 Feb;183:132-141. doi: 10.1016/j.ejpb.2022.12.016. Epub 2022 Dec 30.
Breast cancer is the most common malignant tumor in women, and the liver is the main target organ for breast cancer metastasis. Once metastasis occurs, the prognosis is very poor. The uptake of PSA NPs made by our synthesized Palmitic acid-modified human serum albumin (PSA) in macrophages is about 15 times higher than that of HSA NPs. As a first-line chemotherapeutic drug, paclitaxel not only does not kill macrophages, but it can also polarize macrophages into classically activated macrophages (M1). We combined these two characteristics into PTX-PSA NPs, which achieved dual targeting of macrophages and tumor cells, improved the tumor microenvironment, and achieved a more effective anti-breast cancer drug effect than PTX-HSA NPs. On this basis, we also used the pathological characteristics of low vascular perfusion of breast cancer liver metastasis, and used the characteristics of macrophages that can release paclitaxel after internalizing paclitaxel, and use macrophages as the delivery system of breast cancer liver metastasis. Therefore,PTX-PSA NPs is better than PTX-HSA NPs to achieve anti-breast cancer liver metastasis.
乳腺癌是女性最常见的恶性肿瘤，肝脏是乳腺癌转移的主要靶器官。一旦发生转移，预后非常差。我们合成的棕榈酸修饰人血清白蛋白（PSA）制成的PSA NPs在巨噬细胞中的摄取量比HSA NPs高约15倍。作为一线化疗药物，紫杉醇不仅不杀死巨噬细胞，还能将巨噬细胞极化为经典激活的巨噬细胞（M1）。我们将这两个特性结合到PTX-PSA NPs中，实现了对巨噬细胞和肿瘤细胞的双重靶向，改善了肿瘤微环境，比PTX-HSA NPs实现了更有效的抗乳腺癌药物效果。在此基础上，我们还利用乳腺癌肝转移低血管灌注的病理特征，利用巨噬细胞内化紫杉醇后能释放紫杉醇的特性，将巨噬细胞作为乳腺癌肝转移的递送系统。因此，PTX-PSA NPs比PTX-HSA NPs更能实现抗乳腺癌肝转移。
