Rationale: Ferroptosis is a regulated process of cell death caused by iron-dependent accumulation of lipid hydroperoxides (LPO). It is sensitive to epithelial-to-mesenchymal transition (EMT) cells, a well-known therapy-resistant state of cancer. Previous studies on nanomaterials did not investigate the immense value of ferroptosis therapy (FT) in epithelial cell carcinoma during EMT. Herein, we describe an EMT-specific nanodevice for a comprehensive FT strategy involving LPO burst.Methods: Mitochondrial membrane anchored oxidation/reduction response and Fenton-Reaction-Accelerable magnetic nanophotosensitizer complex self-assemblies loading sorafenib (CSO-SS-Cy7-Hex/SPION/Srfn) were constructed in this study for LPO produced to overcome the therapy-resistant state of cancer. Both in vitro and in vivo experiments were performed using breast cancer cells to investigate the anti-tumor efficacy of the complex self-assemblies.Results: The nano-device enriched the tumor sites by magnetic targeting of enhanced permeability and retention effects (EPR), which were disassembled by the redox response under high levels of ROS and GSH in FT cells. Superparamagnetic iron oxide nanoparticles (SPION) released Fe2+ and Fe3+ in the acidic environment of lysosomes, and the NIR photosensitizer Cy7-Hex anchored to the mitochondrial membrane, combined sorafenib (Srfn) leading to LPO burst, which was accumulated ~18-fold of treatment group in breast cancer cells. In vivo pharmacodynamic test results showed that this nanodevice with small particle size and high cytotoxicity increased Srfn circulation and shortened the period of epithelial cancer treatment.Conclusion: Ferroptosis therapy had a successful effect on EMT cells. These findings have great potential in the treatment of therapy-resistant epithelial cell carcinomas.
Ferroptosis
is an iron-dependent cell death caused by accumulation
of lipid peroxidation (LPO), which is a new strategy for cancer treatment.
Th current ferroptosis therapy nanodevices have low efficiency and
side effects generally. Hence, we developed a Black Hole Quencher
(BHQ)-based fluorescence “off–on” nanophotosensitizer
complex assembly (CSO-BHQ-IR780-Hex/MIONPs/Sor). CSO-connected BHQ-IR780-Hex
and -loaded magnetic iron oxide nanoparticles (MIONPs) and sorafenib
(Sor) formed a very concise functionalized delivery system. CSO-BHQ-IR780-Hex
disassembled by GSH attack and released IR780-Hex, MIONPs, and sorafenib.
IR780-Hex anchored to the mitochondrial membrane, which would contribute
to amplifying the efficiency of the photosensitizer. When NIR irradiation
was given to CSO-BHQ-IR780-Hex/MIONPs/Sor-treated cells, iron supply
increased, the xCT/GSH/GPX-4 system was triggered, and a lot of LPO
burst. A malondialdehyde test showed that LPO in complex assembly-treated
cells was explosive and increased about 18-fold compared to the control.
The accumulation process of particles was monitored by an IR780-Hex
photosensitizer, which showed an excellent tumor target ability by
magnetic of nanodevice in vivo. Interestingly, the half-life of sorafenib
in a nanodevice was increased about 26-fold compared to the control
group. Importantly, the complex assembly effectively inhibits tumor
growth in the breast tumor mouse model. This work would provide ideas
in designing nanomedicines for the ferroptosis treatment of cancer.
Chicoric acid is the main phenolic active ingredient in Echinacea purpurea (Asteraceae), best known for its immune‐enhancing ability, as well as used as a herbal medicine. To achieve further utilization of medicinal ingredients from E. purpurea, an efficient preparative separation of chicoric acid was developed based on macroporous adsorption resin chromatography. The separation characteristics of several different typical macroporous adsorption resins were evaluated by adsorption/desorption column experiments, and HPD100 was revealed as the optimal one, which exhibited that the adsorbents fitted well to the pseudo‐second‐order kinetics model and Langmuir isotherm model, and the optimal process parameters were obtained. The breakthrough curves could be predicted and end‐point could be determined early. Besides, the optimal elution conditions of chicoric acid can be achieved using the quality control methods. As a result, the purity of chicoric acid was increased 15.8‐fold (from 4 to 63%) after the treatment with HPD100. The process of the enrichment and separation of chicoric acid is considerate, because of its high efficiency and simple operation. The established separation and purification method of chicoric acid is expected to be valuable for further utilization of E. purpurea according to product application in pharmaceutical fields in the future.
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