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Biodegradable hollow mesoporous organosilica nanotheranostics (HMON) for multi-mode imaging and mild photo-therapeutic-induced mitochondrial damage on gastric cancer
Yanfeng Hu
Department of general surgery, Nanfang Hospital, Southern Medical University, Guangzhou
Corresponding Author
ORCiD: https://orcid.org/0000-0001-5608-3587
License:
This work is licensed under a CC BY 4.0 License. Read Full License
View the published version at Journal of Nanobiotechnology.
Background: CuS-modified hollow mesoporous organosilica nanoparticles ([email protected]) 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 [email protected]&PDT inducing gastric cancer (GC) cells’ mitochondrial damage, remained unclear. Moreover, theranostic efficiency of [email protected] 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 [email protected]/Gd).
Results: [email protected]/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, [email protected]/Gd could efficiently enter GC cells, induce combined mild PTT (43-45 °C) and PDT under mild NIR power density (0.8W/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 [email protected]/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, [email protected]/Gd could selectively cause mild photo-therapy at cancer region, efficiently inhibit the growth of GC cells without evident systemic toxicity in vivo.
Conclusion: [email protected]/Gd could serve as a promising multifunctional nanotheranostic platform and as a cancer photo-therapy agent through inducing mitochondrial dysfunction on GC.
Keywords
Hollow mesoporous organosilica nanoparticles (HMON); Photo-thermal therapy (PTT); Photo-dynamic therapy (PDT); Multi-modal imaging; Mitochondrial damage
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CURRENT STATUS: Published
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Posted 04 Jun, 2020
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On 20 Jul, 2020
No community comments so far
Editorial decision: Accept
On 26 Jun, 2020
Reviewer #1 agreed
On 21 Jun, 2020
Reviewer #2 agreed
On 21 Jun, 2020
Review #1 received
Received 21 Jun, 2020
Review #2 received
Received 21 Jun, 2020
Reviewers invited
Invitations sent on 01 Jun, 2020
Editor assigned
On 28 May, 2020
Submission checks complete
On 27 May, 2020
Editor invited
On 27 May, 2020
No comments provided
Review #2 received
Received 27 Apr, 2020
Editorial decision: Major revision
On 27 Apr, 2020
Review #3 received
Received 27 Apr, 2020
Reviewer #3 agreed
On 25 Apr, 2020
Review #1 received
Received 25 Apr, 2020
Reviewers invited
Invitations sent on 19 Apr, 2020
Reviewer #1 agreed
On 19 Apr, 2020
Reviewer #2 agreed
On 19 Apr, 2020
Editor assigned
On 13 Apr, 2020
Submission checks complete
On 12 Apr, 2020
Editor invited
On 12 Apr, 2020
First submitted
On 10 Apr, 2020
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This preprint is under consideration at Journal of Nanobiotechnology. A preprint is a preliminary version of a manuscript that has not completed peer review at a journal. Research Square does not conduct peer review prior to posting preprints. The posting of a preprint on this server should not be interpreted as an endorsement of its validity or suitability for dissemination as established information or for guiding clinical practice.
Learn more about In Review
Research
Biodegradable hollow mesoporous organosilica nanotheranostics (HMON) for multi-mode imaging and mild photo-therapeutic-induced mitochondrial damage on gastric cancer
Yanfeng Hu
Department of general surgery, Nanfang Hospital, Southern Medical University, Guangzhou
Corresponding Author
ORCiD: https://orcid.org/0000-0001-5608-3587
Badges
Prescreen
This manuscript passed our Prescreen assessment
Complete author information
Appropriate declaration statements
Potential risks to human health
Prescreen
Peer Review Timeline
CURRENT STATUS: Published
Version 2
Posted 04 Jun, 2020
Published
On 20 Jul, 2020
No community comments so far
Editorial decision: Accept
On 26 Jun, 2020
Reviewer #1 agreed
On 21 Jun, 2020
Reviewer #2 agreed
On 21 Jun, 2020
Review #1 received
Received 21 Jun, 2020
Review #2 received
Received 21 Jun, 2020
Reviewers invited
Invitations sent on 01 Jun, 2020
Editor assigned
On 28 May, 2020
Submission checks complete
On 27 May, 2020
Editor invited
On 27 May, 2020
No comments provided
Review #2 received
Received 27 Apr, 2020
Editorial decision: Major revision
On 27 Apr, 2020
Review #3 received
Received 27 Apr, 2020
Reviewer #3 agreed
On 25 Apr, 2020
Review #1 received
Received 25 Apr, 2020
Reviewers invited
Invitations sent on 19 Apr, 2020
Reviewer #1 agreed
On 19 Apr, 2020
Reviewer #2 agreed
On 19 Apr, 2020
Editor assigned
On 13 Apr, 2020
Submission checks complete
On 12 Apr, 2020
Editor invited
On 12 Apr, 2020
First submitted
On 10 Apr, 2020
Metrics
Comments: 0
PDF Downloads: ...
HTML Views: ...
Subject Areas
Nanoscience
License:
This work is licensed under a CC BY 4.0 License. Read Full License
View the published version at Journal of Nanobiotechnology.
Background: CuS-modified hollow mesoporous organosilica nanoparticles ([email protected]) 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 [email protected]&PDT inducing gastric cancer (GC) cells’ mitochondrial damage, remained unclear. Moreover, theranostic efficiency of [email protected] 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 [email protected]/Gd).
Results: [email protected]/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, [email protected]/Gd could efficiently enter GC cells, induce combined mild PTT (43-45 °C) and PDT under mild NIR power density (0.8W/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 [email protected]/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, [email protected]/Gd could selectively cause mild photo-therapy at cancer region, efficiently inhibit the growth of GC cells without evident systemic toxicity in vivo.
Conclusion: [email protected]/Gd could serve as a promising multifunctional nanotheranostic platform and as a cancer photo-therapy agent through inducing mitochondrial dysfunction on GC.
Figure 1
Figure 2
Figure 3
Figure 4
Figure 5
Figure 6
Figure 7