A pH-sensitive imidazole grafted polymeric micelles nanoplatform based on ROS amplification for ferroptosis-enhanced chemodynamic therapy
Source abstract
Abstract
Highly toxic reactive oxygen species (ROS), crucial in inducing apoptosis and ferroptosis, are pivotal for cell death pathways in cancer therapy. However, the effectiveness of ROS-related tumor therapy is impeded by the limited intracellular ROS and substrates, coupled with the presence of abundant ROS scavengers like glutathione (GSH). In this research, we developed acid-responsive, iron-coordinated polymer nanoparticles (PPA/TF) encapsulating a mitochondrial-targeting drug alpha-tocopheryl succinate (α-TOS) for enhanced synergistic tumor treatment. The imidazole grafted micelles exhibit prolonged blood circulation and improve the delivery efficiency of the hydrophobic drug α-TOS. Additionally, PPA's design aids in delivering Fe3+, supplying ample iron ions for chemodynamic therapy (CDT) and ferroptosis through the attachment of imidazole groups to Fe3+. In the tumor's weakly acidic intracellular environment, PPA/TF facilitates pH-responsive drug release. α-TOS specifically targets mitochondria, generating ROS and replenishing those depleted by the Fenton reaction. Moreover, the presence of Fe3+ in PPA/TF amplifies ROS upregulation, promotes GSH depletion, and induces oxidative damage and ferroptosis, effectively inhibiting tumor growth. This research presents an innovative ROS-triggered amplification platform that optimizes CDT and ferroptosis for effective cancer treatment.
Source: europepmc · Quality: candidate unverified · Source record ↗
Research context
OpenAlex topics: Nanoplatforms for cancer theranostics · Advanced Nanomaterials in Catalysis · Extracellular vesicles in disease
SciVX discovery tags are terminology-based. OpenAlex topics are source-provided classifications.
References (38)
Show source-provided references
1. Reactive oxygen species (ROS)-based nanomedicine10.1021/acs.chemrev.8b00626 ↗
2. Targeting cancer cells by ROS-mediated mechanisms: a radical therapeutic approach?10.1038/nrd2803 ↗
3. Mitochondrial targeting overcomes ABCA1-dependent resistance of lung carcinoma to α-tocopheryl succinate10.1007/s10495-012-0795-1 ↗
4. α-Tocopheryl succinate induces apoptosis by targeting ubiquinone-binding sites in mitochondrial respiratory complex II10.1038/onc.2008.69 ↗
5. Mitochondria-acting carrier-free nanoplatform self-assembled by α-tocopheryl succinate carrying cisplatin for combinational tumor therapy10.1093/rb/rbab029 ↗
6. The role of alpha tocopheryl succinate (α-TOS) as a potential anticancer agent10.1080/01635581.2014.863367 ↗
7. Targeted combination of antioxidative and anti-inflammatory therapy of rheumatoid arthritis using multifunctional Dendrimer-Entrapped gold nanoparticles as a platform10.1002/smll.202005661 ↗
8. A Tumor-specific cascade amplification drug release nanoparticle for overcoming multidrug resistance in cancers10.1002/adma.201702342 ↗
9. Enhanced antitumor efficacy by a cascade of reactive oxygen species generation and drug release10.1002/anie.201908997 ↗
10. Degradable iron-rich mesoporous dopamine as a dual-glutathione depletion nanoplatform for photothermal-enhanced ferroptosis and chemodynamic therapy10.1016/j.jcis.2023.02.041 ↗
11. Biomedicine meets fenton chemistry10.1021/acs.chemrev.0c00977 ↗
12. Heparanase-driven sequential released nanoparticles for ferroptosis and tumor microenvironment modulations synergism in breast cancer therapy10.1016/j.biomaterials.2020.120429 ↗
13. Multi-stimuli-responsive polymer particles, films, and hydrogels for drug delivery10.1016/j.chempr.2018.07.002 ↗
14. Drug-loaded nanogel for efficient orchestration of cell death pathways by intramitochondrial disulfide polymerization
15. Enzyme-responsive branched glycopolymer-based nanoassembly for co-delivery of paclitaxel and akt inhibitor toward synergistic therapy of gastric cancer
16. Responsive assembly of upconversion nanoparticles for pH-activated and near-infrared-triggered photodynamic therapy of deep tumors
17. Radiotherapy-mediated redox homeostasis-controllable nanomedicine for enhanced ferroptosis sensitivity in tumor therapy10.1016/j.actbio.2023.01.022 ↗
18. A self-amplifying nanodrug to manipulate the Janus-faced nature of ferroptosis for tumor therapy10.1039/D1NH00506E ↗
19. Size-dependent EPR effect of polymeric nanoparticles on tumor targeting10.1002/adhm.201901223 ↗
20. Drug release of pH-sensitive poly(L-aspartate)-b-poly(ethylene glycol) micelles with POSS cores10.1039/C3PY00965C ↗
21. A robust method for critical micelle concentration determination using coumarin-6 as a fluorescent probe10.1039/C9AY00577C ↗
22. Reversing chemotherapy resistance by a synergy between lysosomal ph-activated mitochondrial drug delivery and erlotinib-mediated drug efflux inhibition10.1021/acsami.1c03196 ↗
23. A Graphdiyne oxide-based iron sponge with photothermally enhanced tumor-specific fenton chemistry10.1002/adma.202000038 ↗
24. Preparation and evaluation of liposomes co-loaded with doxorubicin, phospholipase D inhibitor 5-fluoro-2-indolyl deschlorohalopemide (FIPI) and D-alpha tocopheryl acid succinate (α-TOS) for anti-metastasis10.1186/s11671-019-2964-4 ↗
25. A multichannel Ca2+ nanomodulator for multilevel mitochondrial destruction-mediated cancer therapy10.1002/adma.202007426 ↗
26. Nanocatalytic tumor therapy by single-atom catalysts
27. Salinomycin kills cancer stem cells by sequestering iron in lysosomes10.1038/nchem.2778 ↗
28. Dual-targeting photosensitizer-peptide amphiphile conjugate for enzyme-triggered drug delivery and synergistic chemo-photodynamic tumor therapy
29. pH responsive coumarin and imidazole grafted polymeric micelles for cancer therapy
30. Endogenous reactive oxygen species burst induced and spatiotemporally controlled multiple drug release by traceable nanoparticles for enhancing antitumor efficacy10.1039/D1BM00668A ↗
31. Poly (ester-thioether) microspheres co-loaded with erlotinib and α-tocopheryl succinate for combinational therapy of non-small cell lung cancer10.1039/C9TB02840D ↗
32. Tumor microenvironment-activatable Fe-doxorubicin preloaded amorphous CaCO3 nanoformulation triggers ferroptosis in target tumor cells10.1126/sciadv.aax1346 ↗
33. Activatable nanomedicine for overcoming hypoxia-induced resistance to chemotherapy and inhibiting tumor growth by inducing collaborative apoptosis and ferroptosis in solid tumors
34. Hyaluronic acid-targeted and pH-responsive drug delivery system based on metal-organic frameworks for efficient antitumor therapy10.1016/j.biomaterials.2019.119473 ↗
35. Tumor microenvironment-responsive yolk–shell NaCl@virus-inspired tetrasulfide-organosilica for ion-interference therapy via osmolarity surge and oxidative stress amplification10.1021/acsnano.1c09496 ↗
36. Potential-independent intracellular drug delivery and mitochondrial targeting10.1021/acsnano.1c09456 ↗
37. In situ generation of hybrid alginate hydrogels for enhanced breast tumor ferrotherapy through multiplex magnifying redox imbalances
38. A reactive oxygen species-replenishing coordination polymer nanomedicine disrupts redox homeostasis and induces concurrent apoptosis-ferroptosis for combinational cancer therapy10.1016/j.actbio.2022.07.055 ↗