Enzyme functionalized PEOz modified magnetic polydopamine with enhanced penetration for cascade-augmented synergistic tumor therapy.

ABSTRACT

In recent years, reactive oxygen species (ROS)-mediated cancer therapies have been widely recognized for their high selectivity and good biological safety. However, due to the difficulties of endogenous tumor microenvironment (TME), penetration of tumor tissues and integration of multimodal tumor ablation, the treatment with traditional therapies could not achieve satisfactory tumor inhibition effects. Here, a doxorubicin (DOX)-glucose oxidase (GOx) dual-loaded and poly (2-ethyl-2-oxazoline) (PEOz) decorated magnetic polydopamine nanoparticles (Fe3O4-DOX@PDA-GOx@PEOz, FDPGP) were constructed for tumor ablation. GOx-mediated cascade enzyme reactions could amplify oxidative stress damage and further synergistically inhibit breast cancer. Its pH-responsive charge reversal, drug-controlled release, photothermal, and cascade reactions were evaluated through extracellular experiments. Cellular uptake, cell cytotoxicity, tumor penetration and therapeutic efficacy of FDPGP were investigated through intracellular experiments. Finally, in vivo distribution, photothermal, synergistic antitumor therapeutic effect and biosafety were evaluated comprehensively by in vivo experiments. Excitingly, outstanding tumor enrichment and penetration, superior anticancer effects and biosafety were achieved by the combination of photothermal therapy (PTT)/starvation therapy (ST)/chemodynamic therapy (CDT)/chemotherapy (CT). As such, the FDPGP nanoplatform provides a new insight into the development of collaboratively multimodal enhanced tumor therapy.