Iron-doxorubicin prodrug loaded liposome nanogenerator programs multimodal ferroptosis for efficient cancer therapy

Abstract

Ferroptosis is a new mode of cell death, which can be induced by Fenton reaction-mediated lipid peroxidation. However, the insufficient H 2 O 2 and high GSH in tumor cells restrict the efficiency of Fenton reaction-dependent ferroptosis. Herein, a self-supplying lipid peroxide nanoreactor was developed to co-delivery of doxorubicin (DOX), iron and unsaturated lipid for efficient ferroptosis. By leveraging the coordination effect between DOX and Fe 3+ , trisulfide bond-bridged DOX dimeric prodrug was actively loaded into the core of the unsaturated lipids-rich liposome via iron ion gradient method. First, Fe 3+ could react with the overexpressed GSH in tumor cells, inducing the GSH depletion and Fe 2+ generation. Second, the cleavage of trisulfide bond could also consume GSH, and the released DOX induces the generation of H 2 O 2, which would react with the generated Fe 2+ in step one to induce efficient Fenton reaction-dependent ferroptosis. Third, the formed Fe 3+ /Fe 2+ couple could directly catalyze peroxidation of unsaturated lipids to boost Fenton reaction-independent ferroptosis. This iron-prodrug liposome nanoreactor precisely programs multimodal ferroptosis by integrating GSH depletion, ROS generation and lipid peroxidation, providing new sights for efficient cancer therapy.

Magnetic Biochar Mediates BDE-153 Accumulation and Metabolism in Rice (Oryza sativa L.) by Modulating Iron Plaque and the Fatty Acid Profile

“…Although IP content had no significant correlation with FA saturation in BDE-153-treated roots as determined by the relationship between IP and SAFA ( R 2 = 0.4305) or USFA ( R 2 = 0.4472) (Figure C), all MBC treatments significantly inhibited UFAs in both shoots and roots as compared to BC, particularly the polyunsaturated fatty acids (PUFA) C18:2 and C18:3 (Figures A,B and S5). The uptake of Fe 2+ from IP or MBC can enhance lipid peroxidation, , and thus, decrease the UFA content in plants. More importantly, IP formation was negatively correlated with MLFA and VLFA, with R 2 values of 0.7626** and 0.9133**, respectively (Figure C).…”

“…Although IP content had no significant correlation with FA saturation in BDE-153-treated roots as determined by the relationship between IP and SAFA (R 2 = 0.4305) or USFA (R 2 = 0.4472) (Figure 2C), all MBC treatments significantly inhibited UFAs in both shoots and roots as compared to BC, particularly the polyunsaturated fatty acids (PUFA) C18:2 and C18:3 (Figures 2A,B and S5). The uptake of Fe 2+ from IP or MBC can enhance lipid peroxidation, 57,58 and thus, decrease the UFA content in 3B), suggesting that IP formation could act as a barrier to prevent BDE-153 accumulation in rice roots. Pi et al also reported that IP acted as a barrier to decrease PAH and PBDE uptake by mangroves, largely by increasing PAH and PBDE accumulation on root surfaces.…”

Electrospun multi‐chamber core–shell nanofibers and their controlled release behaviors: A review

“…In recent decades, nanomaterials have been rapidly used in materials science and engineering applications due to their nano effects during the past decades (Forigua et al, 2021; Gu, Pan, et al, 2022; Rehan et al, 2022; Yang et al, 2021; Yuan, Fan, et al, 2023). Among these remarkable nanomaterials, nanofibers have drawn significant attention due to their diverse physiochemical properties, which could overcome the limitations of the macroscale (Yu & Huang, 2023).…”

Metal‐Organic Framework‐Based Nanomedicines for Ferroptotic Cancer Therapy

“…With the rapid development of nanotechnology in medicine, nano-sized drug delivery systems (NDDS) are promising to address the above issues. [18,19] The typical nanocarriers for drug delivery include liposomes [20] , polymer micelles [21] , and metal nanoparticles [22] . Therefore, NDDS is promising for ferroptotic anticancer drug delivery.…”