Effective tumor diagnosis and therapy using ROS-responsive PEGylated ferrocene polymer nanoparticles

Abstract

Cancer is a major cause of human death worldwide. Therefore, various drugs have been used for chemotherapy. They are usually delivered via a drug-delivery system to enhance their efficacy and stability, so their inherent limitations including water insolubility, instability, and cytotoxicity to be overcome. Recently, a theragnostic has been developed to co-deliver an anticancer drug and imaging agent. This enables a simultaneous diagnosis and therapy of cancer in an early stage. Thus, in this study, Paclitaxel (PTX) and Nile Red (NR) were loaded into a polymeric drug-delivery system to evaluate the inhibitory efficacy of cancer cells. PEG-ferrocene nanoparticles (PFNP) were developed using a polymer containing hydrophobic ferrocene that can be hydrophilic in presence of reactive oxygen species (ROS). The loaded PTX and NR were released by hydrophobic-hydrophilic transition and destruction of polymer micelles. The ROS-responsiveness and stability of PFNP were acquired by optimization of initial molar ratio of monomers, methacrylic acid (MA) and poly(ethylene glycol) methyl ether methacrylate (PEGMA) during their copolymerization with ferrocene units. The physicochemical properties of as-prepared PFNP did not change even after PTX and NR loading. PTX- and NR-loaded PFNP (PTX,NR@PFNP) exhibited the faster release profile of PTX after treatment of oxidant. Accordingly, it had a stronger anticancer activity in ROS-rich cancer cells. than in fibroblast cells with relatively low ROS level. Meanwhile, the biocompatible PFNP did not have any cytotoxic effect. The intracellular uptake of PTX,NR@PFNP localized in cancer cells was monitored by fluorescent intensity of the loaded NR. This facilitates a promising application of PFNP as a theragnostic nano-platform that simultaneously delivers anticancer drug and imaging agent.