Catalytic chemistry of iron-free Fenton nanocatalysts for versatile radical nanotherapeutics

The conversion of nontoxic agents into therapeutic species in situ, just within the disease micro-environment, is the ideal strategy because it can substantially enhance the therapeutic efficacy but mitigate the side effect to normal cells/tissues. The emerging nanocatalytic medicine based on the catalytic Fenton reaction can achieve this goal by triggering a disease-specific catalytic reaction to produce therapeutic reaction oxygen species. Traditional iron-based Fenton nanocatalysts are the dominant agents for triggering in situ reactions and radical nanotherapeutics, but they suffer from low reaction rate and narrow pH operation range, significantly hindering their further biomedical applications and clinical translation. Fortunately, the emergence of iron-free nanocatalysts provides alternative but highly efficient nanoplatforms for achieving desirable Fenton reaction-based nanocatalytic radical therapeutics. This comprehensive review discusses the very-recent progress on the elaborate design, rational construction, purpose-oriented multifunctionalization and catalytic property-performance relationship of iron-free Fenton nanocatalysts (e.g., transition metal-based, precious-metal-based, nonmetal-based nanocatalysts and their composites) for versatile radical nanotherapeutics. The focus is particularly on the underlying catalytic chemistry and mechanism for endowing these iron-free nanocatalysts with unique/specific physicochemical properties for anticancer, antibacterial, antibiofilm and synergistic biomedical applications. Finally, we concentrate on the unresolved critical issues, current challenges and future development direction/prospects of these iron-free Fenton nanocatalysts for future clinical translations.