This is a preprint, 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.
A new preprint design is coming!
We have improved readability, clarity, accessibility, and opportunities for engagement.
Article
Yongxiang Zhao
Guangxi Medical University/National Center for International Research of Bio-targeting Theranostics
Corresponding Author
License:
This work is licensed under a CC BY 4.0 License. Read Full License
In this study we show for the first time that a reduced graphene oxide (rGO) carrier has a 15-fold higher catalysis rate than graphene oxide (GO) in Ag+ reduction. Based on this, we constructed a tumor microenvironment-enabled in situ silver-based electrochemical oncolytic bioreactor (SEOB) which unlocked an Ag+ prodrug to generate silver nanoparticles and inhibited the growth of various tumors. In this bioreactor system, intratumoral H2O2 acted as the reductant and the rGO carrier acted as the catalyst. Chelation of aptamers to this prodrug increased the production of silver nanoparticles by tumor cells, especially in the presence of Vitamin C, which broke down in tumor cells to supply massive amounts of H2O2. Consequently, highly efficient silver nanoparticle-induced apoptosis was observed in HepG2 and A549 cells in vitro and in HepG2- and A549-derived tumors in vivo. The apoptosis was associated with ROS-induced changes in mitochondrial membrane potential and DNA damage. The specific aptamer targeting and intratumoral silver nanoparticle production guaranteed excellent biosafety, with no damage to normal cells, because the Ag+ prodrug was specifically unlocked in tumors. More significantly, there was no evident tissue damage in monkeys, which greatly increases the clinical translation potential of the SEOB system.
Keywords
Silver-based electrochemical oncolytic bioreactor (SEOB), Intratumoral silver-based nanosynthetic prodrug, Primate biosafety, Aptamer targeting
Figure 1
Figure 2
Figure 3
Figure 4
Figure 5
There is NO Competing Interest.
This is a list of supplementary files associated with this preprint. Click to download.
- SupplementaryInformation.doc
Supplementary Figs S1-S12, and partial discussions are included in the supporting information.
- VideoS1.mp4
Video S1 caption: Time-dependent LCSM observation of HepG2 cells (1×106) after incubation with FITC-labeled END-CS/rGO/Ag+-DNA (100 μL, 1 mg/ mL) bioreactors, noting that cells were pre-treated with VitC (100 μl, 1 mg/mL) and PI dye (100 μl, 1 mg/mL) before incubation, with FITC-labeled END-CS/rGO/Ag+-DNA..
- VideoS2.mp4
Video S2 caption: Time-dependent LCSM observation of 293T cells (1×106) after incubation with FITC-labeled END-CS/rGO/Ag+-DNA (100 μL, 1 mg/ mL) bioreactors, noting that cells were pre-treated with VitC (100 μl, 1 mg/mL) and PI dye (100 μl, 1 mg/mL) before incubation, with FITC-labeled END-CS/rGO/Ag+-DNA.
Loading...
Badges
Prescreen
This manuscript passed our Prescreen assessment
Complete author information
Appropriate declaration statements
Potential risks to human health
Prescreen
History
CURRENT STATUS: Posted
Version 1
Posted 16 Nov, 2020
No community comments so far
Metrics
Comments: 0
PDF Downloads: ...
HTML Views: ...
Learn more about our company.
A new preprint design is coming!
We have improved readability, clarity, accessibility, and opportunities for engagement.
This is a preprint, 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.
Article
Yongxiang Zhao
Guangxi Medical University/National Center for International Research of Bio-targeting Theranostics
Corresponding Author
Badges
Prescreen
This manuscript passed our Prescreen assessment
Complete author information
Appropriate declaration statements
Potential risks to human health
Prescreen
History
CURRENT STATUS: Posted
Version 1
Posted 16 Nov, 2020
No community comments so far
Metrics
Comments: 0
PDF Downloads: ...
HTML Views: ...
License:
This work is licensed under a CC BY 4.0 License. Read Full License
In this study we show for the first time that a reduced graphene oxide (rGO) carrier has a 15-fold higher catalysis rate than graphene oxide (GO) in Ag+ reduction. Based on this, we constructed a tumor microenvironment-enabled in situ silver-based electrochemical oncolytic bioreactor (SEOB) which unlocked an Ag+ prodrug to generate silver nanoparticles and inhibited the growth of various tumors. In this bioreactor system, intratumoral H2O2 acted as the reductant and the rGO carrier acted as the catalyst. Chelation of aptamers to this prodrug increased the production of silver nanoparticles by tumor cells, especially in the presence of Vitamin C, which broke down in tumor cells to supply massive amounts of H2O2. Consequently, highly efficient silver nanoparticle-induced apoptosis was observed in HepG2 and A549 cells in vitro and in HepG2- and A549-derived tumors in vivo. The apoptosis was associated with ROS-induced changes in mitochondrial membrane potential and DNA damage. The specific aptamer targeting and intratumoral silver nanoparticle production guaranteed excellent biosafety, with no damage to normal cells, because the Ag+ prodrug was specifically unlocked in tumors. More significantly, there was no evident tissue damage in monkeys, which greatly increases the clinical translation potential of the SEOB system.
Figure 1
Figure 2
Figure 3
Figure 4
Figure 5
There is NO Competing Interest.
This is a list of supplementary files associated with this preprint. Click to download.
- SupplementaryInformation.doc
Supplementary Figs S1-S12, and partial discussions are included in the supporting information.
- VideoS1.mp4
Video S1 caption: Time-dependent LCSM observation of HepG2 cells (1×106) after incubation with FITC-labeled END-CS/rGO/Ag+-DNA (100 μL, 1 mg/ mL) bioreactors, noting that cells were pre-treated with VitC (100 μl, 1 mg/mL) and PI dye (100 μl, 1 mg/mL) before incubation, with FITC-labeled END-CS/rGO/Ag+-DNA..
- VideoS2.mp4
Video S2 caption: Time-dependent LCSM observation of 293T cells (1×106) after incubation with FITC-labeled END-CS/rGO/Ag+-DNA (100 μL, 1 mg/ mL) bioreactors, noting that cells were pre-treated with VitC (100 μl, 1 mg/mL) and PI dye (100 μl, 1 mg/mL) before incubation, with FITC-labeled END-CS/rGO/Ag+-DNA.
Loading...