Tumor-specific cyclic amplification of oxidative stress by disulfide-loaded fluoropolymer nanogels

Amplification of intracellular oxidative stress has been found to be an effective strategy to induce cancer cell death. Herein, the effect of a disulfide, 2,2'-dithiobis(5-aminopyridine) (BAPS), is revealed on depleting glutathione (GSH) circularly and generating superoxide anion (O₂^•-) spontaneously to manipulate intracellular redox homeostasis. Thus, BAPS is able to work as an oxidative stress amplifier in cancer cells with high GSH concentrations and kill them efficiently. Moreover, leveraging a new class of water-soluble fluoropolymers poly(N-(2-((2,2,2-trifluoroethyl)sulfonyl)ethyl)acrylamide) (PFSNM), BAPS, together with oxygen, can be effectively delivered into hypoxic tumor cells through circulation and significantly inhibit the tumor growth. Therefore, BAPS-loaded PFSNM is an oxidative regulation nanosystem with remarkable therapeutic efficacy for chemodynamic therapy.