Ultra-small FePt/siRNA loaded mesoporous silica nanoplatform to deplete cysteine for enhanced ferroptosis in breast tumor therapy
Source abstract
Abstract
Abstract The upregulation of redox systems inside malignant cells provides a powerful shelter against reactive oxygen species (ROS), hampering the antitumor response of ROS-based therapy. To address this issue, we report a strategy of cysteine depletion to block redox systems and enhance ferroptosis (a ROS-induced cell-death pathway) based on a mesoporous silica nanoplatform (sSFP) coloaded with FePt nanoparticles and siRNA. Through responding to high H2O2 in tumor microenvironment, the ferroptosis agent FePt triggered tumor cell ferroptosis via Fe2+-mediated Fenton reaction. In the meanwhile, siRNA released from sSFP interfered the over-expressed system xC– (the cystine/glutamate antiporter) subunit, xCT, in tumor cells and hindered cysteine intake, resulting the disturbance of redox systems including the glutathione redox system and the thioredoxin redox system. For the overexpressed xCT protein in tumor cells and tumor selectivity of Fenton reaction, this nanoplatform provides a high selectivity for destroying tumors. The subcutaneous xenograft model of breast tumor further verified the enhanced therapeutic effect.
Source: openaire · Quality: candidate unverified · Source record ↗
Research context
OpenAlex topics: Ferroptosis and cancer prognosis · Nanoplatforms for cancer theranostics · MicroRNA in disease regulation
SciVX discovery tags are terminology-based. OpenAlex topics are source-provided classifications.
References (32)
Show source-provided references
1. Modulation of oxidative stress as an anticancer strategy10.1038/nrd4002 ↗
2. Amplification of oxidative stress by a dual stimuli-responsive hybrid drug enhances cancer cell death10.1038/ncomms7907 ↗
3. Ferroptosis: an iron-dependent form of nonapoptotic cell death10.1016/j.cell.2012.03.042 ↗
4. Emerging strategies of cancer therapy based on ferroptosis
5. Ultrasmall nanoparticles induce ferroptosis in nutrient-deprived cancer cells and suppress tumour growth10.1038/nnano.2016.164 ↗
6. Fenton-reaction-acceleratable magnetic nanoparticles for ferroptosis therapy of orthotopic brain tumors10.1021/acsnano.8b06201 ↗
7. Tumor-targeted cascade nanoreactor based on metal–organic frameworks for synergistic ferroptosis–starvation anticancer therapy10.1021/acsnano.9b07789 ↗
8. Engineering magnetosomes for ferroptosis/immunomodulation synergism in cancer10.1021/acsnano.9b00892 ↗
9. Arginine-rich manganese silicate nanobubbles as a ferroptosis-inducing agent for tumor-targeted theranostics10.1021/acsnano.8b06399 ↗
10. Development of a novel FePt-based multifunctional ferroptosis agent for high-efficiency anticancer therapy10.1039/C8NR05150J ↗
11. Tumor‐microenvironment‐triggered ion exchange of a metal–organic framework hybrid for multimodal imaging and synergistic therapy of tumors
12. H2O2-responsive liposomal nanoprobe for photoacoustic inflammation imaging and tumor theranostics via in vivo chromogenic assay10.1073/pnas.1701976114 ↗
13. Oncogene-induced Nrf2 transcription promotes ROS detoxification and tumorigenesis10.1038/nature10189 ↗
14. Glutathione and thioredoxin antioxidant pathways synergize to drive cancer initiation and progression10.1016/j.ccell.2014.11.019 ↗
15. Selective targeting of the cysteine proteome by thioredoxin and glutathione redox systems10.1074/mcp.M113.030437 ↗
16. Targeting the thioredoxin system for cancer therapy10.1016/j.tips.2017.06.001 ↗
17. Glutathione metabolism in cancer progression and treatment resistance10.1083/jcb.201804161 ↗
18. Amplification of tumor oxidative stresses with liposomal fenton catalyst and glutathione inhibitor for enhanced cancer chemotherapy and radiotherapy10.1021/acs.nanolett.8b03905 ↗
19. Specific generation of singlet oxygen through the russell mechanism in hypoxic tumors and GSH depletion by Cu‐TCPP nanosheets for cancer therapy10.1002/anie.201903981 ↗
20. Simultaneous Fenton-like ion delivery and glutathione depletion by MnO2-based nanoagent to enhance chemodynamic therapy10.1002/anie.201712027 ↗
21. System xc− and thioredoxin reductase 1 cooperatively rescue glutathione deficiency10.1074/jbc.M110.121327 ↗
22. Loss of thioredoxin reductase 1 renders tumors highly susceptible to pharmacologic glutathione deprivation10.1158/0008-5472.CAN-10-1509 ↗
23. Systemic depletion of L-cyst(e)ine with cyst(e)inase increases reactive oxygen species and suppresses tumor growth10.1038/nm.4232 ↗
24. Glutamine sensitivity analysis identifies the xCT antiporter as a common triple-negative breast tumor therapeutic target10.1016/j.ccr.2013.08.020 ↗
25. Cystine–glutamate antiporter xCT deficiency suppresses tumor growth while preserving antitumor immunity10.1073/pnas.1814932116 ↗
26. Anion assisted synthesis of large pore hollow dendritic mesoporous organosilica nanoparticles: understanding the composition gradient10.1021/acs.chemmater.5b03963 ↗
27. Enhanced sequestration of selenite in water by nanoscale zero valent iron immobilization on carbon nanotubes by a combined batch, XPS and XAFS investigation10.1016/j.carbon.2015.12.013 ↗
28. Monodisperse FePt nanoparticles and ferromagnetic FePt nanocrystal superlattices10.1126/science.287.5460.1989 ↗
29. RTCGAToolbox: a new tool for exporting TCGA firehose data10.1371/journal.pone.0106397 ↗
30. limma powers differential expression analyses for RNA-sequencing and microarray studies10.1093/nar/gkv007 ↗
31. GSVA: gene set variation analysis for microarray and RNA-Seq data10.1186/1471-2105-14-7 ↗
32. Controlled synthesis of a core-shell nanohybrid for effective multimodal image-guided combined photothermal/photodynamic therapy of tumors10.1038/s41427-019-0164-4 ↗