有效递送药物至实体瘤仍然是一个挑战。HER2阳性（HER2 + ）肿瘤是一种侵略性癌症亚型，对治疗有抵抗性，高复发风险和预后不良。尽管纳米医学技术在肿瘤治疗中显示出明显的优势，但其潜在的临床应用仍受到递送效果和治疗效果不尽如人意的阻碍。本研究基于聚（乳酸-羟基乙酸）（PLGA）纳米粒子和工程修饰的巨噬细胞膜的共聚装体，开发出一种基于基因重编程的巨噬细胞膜包裹的药物载药纳米平台，用于HER2阳性（HER2 + ）癌症治疗。在这个纳米平台中，近红外（NIR）荧光染料ICG或化疗药物多柔比星（DOX）被装载到PLGA核心中，同时抗HER2 affibody稳定表达在巨噬细胞的膜上。与传统巨噬细胞膜涂层的纳米颗粒相比，ICG / DOX @ AMNP纳米颗粒武装有抗HER2 affibody，在体外和体内均显示出良好的HER2靶向能力。小动物成像研究证实了药物递送的改善药代动力学和ICG / DOX @ AMNPs在HER2阳性（HER2 + ）肿瘤中的特异性分布。从机制上讲，与DOX @ NPs或DOX @ MNPs纳米颗粒相比，DOX @ AMNPs通过诱导细胞凋亡和阻断PI3K / AKT信号通路，呈现出协同抑制HER2阳性（HER2 + ）癌细胞或小鼠肿瘤生长的作用。总之，本研究提出了一种有前途的仿生纳米平台，用于高效地将化疗药物靶向递送至HER2阳性（HER2 + ）肿瘤，展示了其在实体瘤治疗中的巨大潜力。

Efficient drug delivery to solid tumors remains a challenge. HER2-positive (HER2+) tumors are an aggressive cancer subtype with a resistance to therapy, high risk of relapse, and poor prognosis. Although nanomedicine technology shows obvious advantages in tumor treatment, its potential clinical translation is still impeded by the unsatisfactory delivery and therapeutic efficacy. In this study, a gene reprogramming macrophage membrane-encapsulated drug-loading nanoplatform was developed for HER2+ cancer therapy based on the co-assembly of poly (lactic-co-glycolic acid) (PLGA) nanoparticles and engineered modified macrophage membranes. In this nanoplatform, near-infrared (NIR) fluorescent dye ICG or chemotherapeutic drug doxorubicin (DOX) was loaded into the PLGA cores, and an anti-HER2 affibody was stably expressed on the membrane of macrophages. In comparison to the nanoparticles with conventional macrophage membrane coating, the ICG/DOX@AMNP nanoparticles armed with anti-HER2 affibody showed excellent HER2-targeting ability both in vitro and in vivo. Small animal imaging studies confirmed the improved pharmacokinetics of drug delivery and specific distribution of the ICG/DOX@AMNPs in HER2+ tumors. Mechanistically, compared with DOX@NPs or DOX@MNPs nanoparticles, DOX@AMNPs exhibited synergistic inhibition of HER2+ cancer cells or mice tumor growth by inducing apoptosis and blocking the PI3K/AKT signaling pathway. Altogether, this study proposes a promising biomimetic nanoplatform for the efficient targeted delivery of chemotherapeutic agents to HER2+ tumors, demonstrating its great potential for solid tumor therapy.