Hierarchical nanoclusters with programmed disassembly for mitochondria-targeted tumor therapy with MR imaging
| Autor: | Huiyang Wang, Yongjun Wu, Gaorong Han, Yifan Wang, Dong Cen, Xiang Li, Congkun Xie |
|---|---|
| Rok vydání: | 2021 |
| Předmět: |
Tumor microenvironment
Biomedical Engineering Hydrogen Peroxide Glutathione Mitochondrion medicine.disease_cause Magnetic Resonance Imaging Nanocapsules Mitochondria Cell biology chemistry.chemical_compound chemistry In vivo Tumor progression Neoplasms Tumor Microenvironment medicine Humans General Materials Science Carcinogenesis Oxidative stress |
| Zdroj: | Biomaterials Science. 9:8189-8201 |
| ISSN: | 2047-4849 2047-4830 |
| Popis: | Mitochondria are crucial metabolic organelles involved in tumorigenesis and tumor progression, and the induction of abnormal mitochondria metabolism is recognized as a strategy with strong potential for the exploration of advanced tumor therapeutics. Herein, hierarchical manganese silicate nanoclusters modified with triphenylphosphonium (MSNAs-TPP) were designed and synthesized for mitochondria-targeted tumor theranostics. The as-prepared MSNAs-TPP retains considerable dimensional and structural stability in the neutral physiological environment, favoring its accumulation at the tumor site. More interestingly, MSNAs-TPP may disassemble in a responsive manner to an acidic tumor microenvironment into ultrasmall manganese silicate nanocapsules (∼6 nm), enabling deep tumor penetration and mitochondria targeting. When reaching the mitochondria, the nanocapsules effectively deplete mitochondrial glutathione (GSH), and simultaneously release catalytic Mn2+ ions to induce amplified oxidative stress in the structure with the enriched CO2 and H2O2 from mitochondria metabolism. As a result, MSNAs-TPP presents considerable antitumor effect without a clear side effect, both in vitro and in vivo. The study may provide an alternative concept in the development of intelligent nanotherapeutics for tumor treatment with high efficacy. |
| Databáze: | OpenAIRE |
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