Oh Hyeryeon, Jeong Eunjin, Lee Jin Sil, Kim Jisu, Lee Donghyun, Kim Byoung Soo, Sung Daekyung, Koo Heebeom, Choi Won Il, Tae Giyoong
Center for Bio-Healthcare Materials, Bio-Convergence Materials R&D Division, Korea Institute of Ceramic Engineering and Technology, Cheongju, 28160, Republic of Korea.
School of Materials Science and Engineering, Gwangju Institute of Science and Technology, Gwangju, 61005, Republic of Korea.
Mater Today Bio. 2023 Aug 18;22:100774. doi: 10.1016/j.mtbio.2023.100774. eCollection 2023 Oct.
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 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.
基于二茂铁的纳米颗粒作为抗癌药物和成像剂的活性氧（ROS）响应性纳米载体已引起关注。然而，由于其生理稳定性较差，它们的生物医学应用仍然有限。纳米载体的聚乙二醇化可提高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响应性的新型聚乙二醇-二茂铁纳米颗粒（PFNPs），用于递送紫杉醇（PTX）和成像剂。聚乙二醇化提高了二茂铁纳米颗粒的稳定性，抑制了它们的ROS响应性破坏。设计了几种含有不同摩尔比甲基丙烯酸和聚（乙二醇）甲基丙烯酸甲酯的聚乙二醇-二茂铁聚合物进行优化。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。PFNPs在ROS存在下在8小时内膨胀，有效释放包封的PTX和成像剂。此外，它们保持稳定，在水溶液和生物缓冲液中储存后其流体动力学直径和多分散指数没有变化。PFNPs在肿瘤模型中的积累比游离染料高15倍。负载PTX的PFNPs显示出显著的肿瘤抑制作用，将肿瘤大小减小到相应对照组的约18%。这些发现表明ROS响应性PFNPs作为抗癌药物和成像剂的生物相容性纳米载体在肿瘤治疗中具有广阔的应用前景。
