基于二茂铁的纳米颗粒已引起人们对其作为活性氧（ROS）响应型抗癌药物和成像剂的纳米载体的兴趣。然而，由于其生理稳定性差，其生物医学应用仍然有限。纳米载体的PEG化改善了其稳定性和生物相容性。在本研究中，我们旨在开发具有增强稳定性和ROS响应性的新型PEG-二茂铁纳米颗粒（PFNPs），用于紫杉醇（PTX）和成像剂的传递。PEG化改善了二茂铁纳米颗粒的稳定性，抑制了其ROS响应性破坏。设计了含有不同摩尔比的丙烯酸甲基酯和聚（乙二醇）甲醚甲基丙烯酸酯的几种PEG-二茂铁聚合物以进行优化。具有最佳单体比例的ROS响应性聚合物自组装成具有增强稳定性的PFNPs。在存在ROS的情况下，8小时内，PFNPs膨胀并有效释放包装的PTX和成像剂。此外，在水溶液和生物缓冲液中储存后，其在流体动力学直径和聚分散度指数方面保持稳定。在体内肿瘤模型中，PFNPs的积累量比自由染料高15倍。装载PTX的PFNPs显示出显著的抑制肿瘤效果，将肿瘤大小减小到对应的对照组的大约18%。这些发现表明ROS响应性PFNPs作为生物相容性抗癌药物和成像剂的纳米载体，在肿瘤治疗中具有潜在的应用前景。© 2023 The Authors. Published by Elsevier Ltd.

Ferrocene-based nanoparticles have garnered interest as reactive oxygen species (ROS)-responsive nanocarriers of anticancer drugs and imaging agents. However, their biomedical applications remain limited due to their poor physiological stability. PEGylation of nanocarriers improves their stability and biocompatibility. In this study, we aimed to develop novel PEG-ferrocene nanoparticles (PFNPs) with enhanced stability and ROS responsiveness for the delivery of paclitaxel (PTX) and imaging agents. PEGylation improved the stability of ferrocene nanoparticles, inhibiting their ROS-responsive destruction. Several PEG-ferrocene polymers containing different molar ratios of methacrylic acid and poly (ethylene glycol) methyl ether methacrylate was designed for optimization. ROS-responsive polymers with optimal monomer ratios were self-assembled into PFNPs with enhanced stability. The PFNPs distended, effectively releasing encapsulated PTX and imaging agents within 8 h in the presence of ROS. Furthermore, they remained stable, with no changes in their hydrodynamic diameters or polydispersity indexes after storage in an aqueous solution and biological buffer. The accumulation of PFNPs in a tumor model in vivo was 15-fold higher than a free dye. PTX-loaded PFNPs showed a substantial tumor-suppression effect, reducing tumor size to approximately 18% of that in the corresponding control group. These findings suggest a promising application of ROS-responsive PFNPs in tumor treatment as biocompatible nanocarriers of anticancer drugs and imaging agents.© 2023 The Authors. Published by Elsevier Ltd.