Recent advances in enhancing reactive oxygen species based chemodynamic therapy

Chemodynamic therapy (CDT), defined as an in situ oxidative stress response catalyzed by the Fenton or Fenton-like reactions to generate cytotoxic hydroxyl radicals (•OH) at tumor sites, exhibits conspicuous inhibition of tumor growth. It has attracted extensive attention for its outstanding edge in effectiveness, lower systemic toxicity and side effects, sustainability, low cost and convenience. However, the inconformity of harsh Fenton reaction conditions and tumor microenvironment hamper its further development, based on which, numerous researchers have made efforts in further improving the efficiency of CDT. In this review, we expounded antitumor capacity of CDT in mechanism, together with its limitation, and then summarized and came up with several strategies to enhance CDT involved tumor therapy strategies by 1) improving catalytic efficiency; 2) increasing hydrogen peroxide levels at tumor sites; 3) reducing glutathione levels at tumor sites; 4) applying external energy intervention; 5) amplifying the distribution of hydroxyl radicals at tumor sites; and 6) combination therapy. Eventually, the perspectives and challenges of CDT are further discussed to encourage more in-depth studies and rational reflections.