Macrophages exosomes-coated Fe3O4 nanoparticles for oxygen independent generation of free radicals and hypoxic cancer therapy

Free radicals, such as H 2 O 2 , O 2 ˉ, •OH, have been extensively applied for cancer therapy. However, their generation is significantly limited due to the hypoxic environment of the tumor. Here, macrophages exosomes coated Fe 3 O 4 nanoparticles loaded with 2,2'-Azobisisoheptonitrile (ABVN) (Fe 3 O 4 -ABVN@Exo NPs) were fabricated to realize photothermally controlled generation of radicals for cancer therapy in an oxygen-independent manner. Upon the irradiation of near infrared light, Fe 3 O 4 generated heat and triggered the release and decomposition of ABVN to produce alkyl radicals, which could damage the DNA, protein, and cause the death of the cells. While the macrophages exosomes could improve the targeting effect and prevent the premature release of ABVN. The nanoparticles indicated a favorable antitumor effect in hypoxic environment, holding a great potential for cancer therapy. A schematic diagram of the fabrication of Fe 3 O 4 -ABVN@Exo NPs and generation of free radicals upon irradiation by a NIR laser. • An initiator, 2,2'-Azobisisoheptonitrile (ABVN), was used as radical generator to be loaded onto Fe 3 O 4 NPs to form Fe 3 O 4 -ABVN NPs for hypoxic cancer therapy in an oxygen-independent manner. • The Fe 3 O 4 -ABVN NPs were encapsulated by exosomes (Fe 3 O 4 -ABVN@Exo NPs) to prevent the premature release and improve the targeting effect. • The free radicals and photothermal effect exhibited synergistic antitumor effect.