Biodegradable hollow mesoporous organosilica nanotheranostics (HMON) for multi-mode imaging and mild photo-therapeutic-induced mitochondrial damage on gastric cancer
BACKGROUND: CuS-modified hollow mesoporous organosilica nanoparticles (HMONCuS) have been preferred as non-invasive treatment for cancer, as near infrared (NIR)-induced photo-thermal effect (PTT) and/or photo-dynamic effect (PDT) could increase cancer cells' apoptosis. However, the certain role of HMON@CuS-produced-PTT&PDT inducing gastric cancer (GC) cells' mitochondrial damage, remained unclear. Moreover, theranostic efficiency of HMON@CuS might be well improved by applying multi-modal imaging, which could offer an optimal therapeutic region and time window. Herein, new nanotheranostics agents were reported by Gd doped HMON decorated by CuS nanocrystals (called HMON@CuS/Gd).
RESULTS: HMONCuS/Gd exhibited appropriate size distribution, good biocompatibility, L-Glutathione (GSH) responsive degradable properties, high photo-thermal conversion efficiency (82.4%) and a simultaneous reactive oxygen species (ROS) generation effect. Meanwhile, HMON@CuS/Gd could efficiently enter GC cells, induce combined mild PTT (43-45 °C) and PDT under mild NIR power density (0.8 W/cm2). Surprisingly, it was found that PTT might not be the only factor of cell apoptosis, as ROS induced by PDT also seemed playing an essential role. The NIR-induced ROS could attack mitochondrial transmembrane potentials (MTPs), then promote mitochondrial reactive oxygen species (mitoROS) production. Meanwhile, mitochondrial damage dramatically changed the expression of anti-apoptotic protein (Bcl-2) and pro-apoptotic protein (Bax). Since that, mitochondrial permeability transition pore (mPTP) was opened, followed by inducing more cytochrome c (Cyto C) releasing from mitochondria into cytosol, and finally activated caspase-9/caspase-3-depended cell apoptosis pathway. Our in vivo data also showed that HMON@CuS/Gd exhibited good fluorescence (FL) imaging (wrapping fluorescent agent), enhanced T1 imaging under magnetic resonance imaging (MRI) and infrared thermal (IRT) imaging capacities. Guided by FL/MRI/IRT trimodal imaging, HMON@CuS/Gd could selectively cause mild photo-therapy at cancer region, efficiently inhibit the growth of GC cells without evident systemic toxicity in vivo.
CONCLUSION: HMONCuS/Gd could serve as a promising multifunctional nanotheranostic platform and as a cancer photo-therapy agent through inducing mitochondrial dysfunction on GC.
| Medienart: |
E-Artikel |
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| Erscheinungsjahr: |
2020 |
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| Erschienen: |
2020 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:18 |
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| Enthalten in: |
Journal of nanobiotechnology - 18(2020), 1 vom: 20. Juli, Seite 99 |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Guo, Weihong [VerfasserIn] |
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| Links: |
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| Anmerkungen: |
Date Completed 22.02.2021 Date Revised 22.02.2021 published: Electronic Citation Status MEDLINE |
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| doi: |
10.1186/s12951-020-00653-y |
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| funding: |
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| Förderinstitution / Projekttitel: |
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| PPN (Katalog-ID): |
NLM31266396X |
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| 245 | 1 | 0 | |a Biodegradable hollow mesoporous organosilica nanotheranostics (HMON) for multi-mode imaging and mild photo-therapeutic-induced mitochondrial damage on gastric cancer |
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| 500 | |a Date Revised 22.02.2021 | ||
| 500 | |a published: Electronic | ||
| 500 | |a Citation Status MEDLINE | ||
| 520 | |a BACKGROUND: CuS-modified hollow mesoporous organosilica nanoparticles (HMONCuS) have been preferred as non-invasive treatment for cancer, as near infrared (NIR)-induced photo-thermal effect (PTT) and/or photo-dynamic effect (PDT) could increase cancer cells' apoptosis. However, the certain role of HMON@CuS-produced-PTT&PDT inducing gastric cancer (GC) cells' mitochondrial damage, remained unclear. Moreover, theranostic efficiency of HMON@CuS might be well improved by applying multi-modal imaging, which could offer an optimal therapeutic region and time window. Herein, new nanotheranostics agents were reported by Gd doped HMON decorated by CuS nanocrystals (called HMON@CuS/Gd) | ||
| 520 | |a RESULTS: HMONCuS/Gd exhibited appropriate size distribution, good biocompatibility, L-Glutathione (GSH) responsive degradable properties, high photo-thermal conversion efficiency (82.4%) and a simultaneous reactive oxygen species (ROS) generation effect. Meanwhile, HMON@CuS/Gd could efficiently enter GC cells, induce combined mild PTT (43-45 °C) and PDT under mild NIR power density (0.8 W/cm2). Surprisingly, it was found that PTT might not be the only factor of cell apoptosis, as ROS induced by PDT also seemed playing an essential role. The NIR-induced ROS could attack mitochondrial transmembrane potentials (MTPs), then promote mitochondrial reactive oxygen species (mitoROS) production. Meanwhile, mitochondrial damage dramatically changed the expression of anti-apoptotic protein (Bcl-2) and pro-apoptotic protein (Bax). Since that, mitochondrial permeability transition pore (mPTP) was opened, followed by inducing more cytochrome c (Cyto C) releasing from mitochondria into cytosol, and finally activated caspase-9/caspase-3-depended cell apoptosis pathway. Our in vivo data also showed that HMON@CuS/Gd exhibited good fluorescence (FL) imaging (wrapping fluorescent agent), enhanced T1 imaging under magnetic resonance imaging (MRI) and infrared thermal (IRT) imaging capacities. Guided by FL/MRI/IRT trimodal imaging, HMON@CuS/Gd could selectively cause mild photo-therapy at cancer region, efficiently inhibit the growth of GC cells without evident systemic toxicity in vivo | ||
| 520 | |a CONCLUSION: HMONCuS/Gd could serve as a promising multifunctional nanotheranostic platform and as a cancer photo-therapy agent through inducing mitochondrial dysfunction on GC | ||
| 650 | 4 | |a Journal Article | |
| 650 | 4 | |a Hollow mesoporous organosilica nanoparticles (HMON) | |
| 650 | 4 | |a Mitochondrial damage | |
| 650 | 4 | |a Multi-modal imaging | |
| 650 | 4 | |a Photo-dynamic therapy (PDT) | |
| 650 | 4 | |a Photo-thermal therapy (PTT) | |
| 650 | 7 | |a Antineoplastic Agents |2 NLM | |
| 650 | 7 | |a Organosilicon Compounds |2 NLM | |
| 650 | 7 | |a Copper Sulfate |2 NLM | |
| 650 | 7 | |a LRX7AJ16DT |2 NLM | |
| 700 | 1 | |a Chen, Zhian |e verfasserin |4 aut | |
| 700 | 1 | |a Chen, Jiajia |e verfasserin |4 aut | |
| 700 | 1 | |a Feng, Xiaoli |e verfasserin |4 aut | |
| 700 | 1 | |a Yang, Yang |e verfasserin |4 aut | |
| 700 | 1 | |a Huang, Huilin |e verfasserin |4 aut | |
| 700 | 1 | |a Liang, Yanrui |e verfasserin |4 aut | |
| 700 | 1 | |a Shen, Guodong |e verfasserin |4 aut | |
| 700 | 1 | |a Liang, Yu |e verfasserin |4 aut | |
| 700 | 1 | |a Peng, Chao |e verfasserin |4 aut | |
| 700 | 1 | |a Li, Yanbing |e verfasserin |4 aut | |
| 700 | 1 | |a Li, Guoxin |e verfasserin |4 aut | |
| 700 | 1 | |a Huang, Wenhua |e verfasserin |4 aut | |
| 700 | 1 | |a Zhao, Bingxia |e verfasserin |4 aut | |
| 700 | 1 | |a Hu, Yanfeng |e verfasserin |4 aut | |
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| 773 | 1 | 8 | |g volume:18 |g year:2020 |g number:1 |g day:20 |g month:07 |g pages:99 |
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