Biological activation of Fenton reaction in polymeric nanoreactors driven by ferrocene-containing membranes: a microenvironment dependent study†

Abstract

Nanocatalytic medicine for treating cancer requires effective, versatile and novel tools and approaches to significantly improve the therapeutic efficiency for the interactions of (non-)enzymatic reactions. However, it is necessary to develop (non-)enzymatic nanotechnologies capable of selectively killing tumour cells without harming normal cells. Their therapeutic characteristics should be the adaption of tumours’ extra- and intracellular environment to being specifically active. To contribute to this common goal, we propose the use of pH- and redox-responsive ferrocene containing polymersomes (FcPsomes). This allows the regulation of their biological activities for the controlled production of radicals via the Fenton reaction and the transport and release of cargo molecules via (destroying) host–guest interactions. This is provided by the Fc-membrane composition of FcPsomes showing different pH responsive active membrane, meaning the membrane permeability is triggering the Fenton reaction. The modulation of radical production is validated by various spectroscopic techniques. Moreover, these nanocontainers allow biological action of glucose oxidase (GOx) as therapeutic enzyme to produce glucono-1,5-lactone as proton source and hydrogen peroxide, initiating the Fenton reaction, in their interior. This provides a synergistic cancer therapeutic treatment for the starvation of hydrogen peroxide, but also ROS-mediated chemodynamic therapy at defined pH values. By modulating membrane permeability, we achieve environmentally regulated and locally driven therapeutic activity in the confinement of FcPsomes, ensuring specificity and safety treatments. The versatility of this platform extends beyond their specific application, allowing for their beneficial therapeutic use, for example, in signaling pathways of cells through the integration of various enzymes in FcPsomes.