ROS-responsive PEGylated ferrocene polymer nanoparticles with improved stability for tumor-selective chemotherapy and imaging

Hyeryeon Oh; Eunjin Jeong; Jin Sil Lee; Jisu Kim; Donghyun Lee; Byoung Soo Kim; Daekyung Sung; Heebeom Koo; Won Il Choi; Giyoong Tae

doi:10.1016/j.mtbio.2023.100774

ROS-responsive PEGylated ferrocene polymer nanoparticles with improved stability for tumor-selective chemotherapy and imaging

Mater Today Bio. 2023 Aug 18:22:100774. doi: 10.1016/j.mtbio.2023.100774. eCollection 2023 Oct.

Authors

Hyeryeon Oh^{1

2}, Eunjin Jeong³, Jin Sil Lee^{1

2}, Jisu Kim¹, Donghyun Lee³, Byoung Soo Kim¹, Daekyung Sung¹, Heebeom Koo³, Won Il Choi¹, Giyoong Tae²

Affiliations

¹ Center for Bio-Healthcare Materials, Bio-Convergence Materials R&D Division, Korea Institute of Ceramic Engineering and Technology, Cheongju, 28160, Republic of Korea.
² School of Materials Science and Engineering, Gwangju Institute of Science and Technology, Gwangju, 61005, Republic of Korea.
³ Department of Medical Life Sciences, Department of Biomedicine & Health Sciences, and Catholic Photomedicine Research Institute, College of Medicine, The Catholic University of Korea, Seoul, 06591, Republic of Korea.

Abstract

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.

Keywords: Cancer therapy; Ferrocene polymer; Imaging; Nanotherapeutic; PEGylation; ROS-responsive.