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.
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Research
Yongyong Li
Tongji University Affiliated Shanghai Pulmonary Hospital
Corresponding Author
ORCiD: https://orcid.org/0000-0002-6688-5978
License:
This work is licensed under a CC BY 4.0 License. Read Full License
Lactate plays a critical role in tumorigenesis, invasion and metastasis. Exhausting lactate in tumors holds great promise for the reversal of the immunosuppressive tumor microenvironment (TME). Herein, we report on a “lactate treatment plant” (i.e., nanofactory) that can dynamically trap pro-tumor lactate and in situ transformation into anti-tumor cytotoxic reactive oxygen species (ROS) for a synergistic chemodynamic and metabolic therapy. To this end, lactate oxidase (LOX) was nano-packaged by cationic polyethyleneimine (PEI), assisted by a necessary amount of copper ions (PLNPCu). As a reservoir of LOX, the tailored system can actively trap lactate through the cationic PEI component to promote lactate degradation by two-fold efficiency. More importantly, the byproducts of lactate degradation, hydrogen peroxide (H2O2), can be transformed into anti-tumor ROS catalyzing by copper ions, mediating an immunogenic cell death (ICD). With the remission of immunosuppressive TME, ICD process effectively initiated the positive immune response in 4T1 tumor model (88% tumor inhibition). This work provides a novel strategy that rationally integrates metabolic therapy and chemodynamic therapy (CDT) for combating tumors.
Keywords
lactate, immunosuppressive tumor microenvironment, immunogenic cell death, chemodynamic therapy
Figure 1
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This is a list of supplementary files associated with this preprint. Click to download.
- GraphicalabstractimageJouranlofnanobiotechnology.png
Scheme 1 Schematic illustration of the lactate exhaustion process of PLNPCu nanosystem through extracellular lactate active-adsorption and establishment of the intracellular lactate treatment plant.
- scheme2.png
Scheme 2 Schematic illustration of the PLNPCu nanofactory closed-loop for lactate consumption and conversion.
- SupportingInformationJournalofnanobiotechnology.docx
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CURRENT STATUS: Under Review
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Posted 12 Oct, 2021
No community comments so far
Review #4 received
Received 29 Oct, 2021
Editorial decision: Major revision
On 29 Oct, 2021
Review #3 received
Received 26 Oct, 2021
Review #2 received
Received 13 Oct, 2021
Review #1 received
Received 12 Oct, 2021
Reviewer #4 agreed
On 11 Oct, 2021
Reviewer #3 agreed
On 08 Oct, 2021
Reviewer #2 agreed
On 08 Oct, 2021
Reviewer #1 agreed
On 07 Oct, 2021
Reviewers invited
Invitations sent on 06 Oct, 2021
Editor assigned
On 06 Oct, 2021
Submission checks complete
On 06 Oct, 2021
Editor invited
On 06 Oct, 2021
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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
Yongyong Li
Tongji University Affiliated Shanghai Pulmonary Hospital
Corresponding Author
ORCiD: https://orcid.org/0000-0002-6688-5978
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: Under Review
Version 1
Posted 12 Oct, 2021
No community comments so far
Review #4 received
Received 29 Oct, 2021
Editorial decision: Major revision
On 29 Oct, 2021
Review #3 received
Received 26 Oct, 2021
Review #2 received
Received 13 Oct, 2021
Review #1 received
Received 12 Oct, 2021
Reviewer #4 agreed
On 11 Oct, 2021
Reviewer #3 agreed
On 08 Oct, 2021
Reviewer #2 agreed
On 08 Oct, 2021
Reviewer #1 agreed
On 07 Oct, 2021
Reviewers invited
Invitations sent on 06 Oct, 2021
Editor assigned
On 06 Oct, 2021
Submission checks complete
On 06 Oct, 2021
Editor invited
On 06 Oct, 2021
First submitted
On 01 Oct, 2021
Metrics
Comments: 0
PDF Downloads: ...
HTML Views: ...
License:
This work is licensed under a CC BY 4.0 License. Read Full License
Lactate plays a critical role in tumorigenesis, invasion and metastasis. Exhausting lactate in tumors holds great promise for the reversal of the immunosuppressive tumor microenvironment (TME). Herein, we report on a “lactate treatment plant” (i.e., nanofactory) that can dynamically trap pro-tumor lactate and in situ transformation into anti-tumor cytotoxic reactive oxygen species (ROS) for a synergistic chemodynamic and metabolic therapy. To this end, lactate oxidase (LOX) was nano-packaged by cationic polyethyleneimine (PEI), assisted by a necessary amount of copper ions (PLNPCu). As a reservoir of LOX, the tailored system can actively trap lactate through the cationic PEI component to promote lactate degradation by two-fold efficiency. More importantly, the byproducts of lactate degradation, hydrogen peroxide (H2O2), can be transformed into anti-tumor ROS catalyzing by copper ions, mediating an immunogenic cell death (ICD). With the remission of immunosuppressive TME, ICD process effectively initiated the positive immune response in 4T1 tumor model (88% tumor inhibition). This work provides a novel strategy that rationally integrates metabolic therapy and chemodynamic therapy (CDT) for combating tumors.
Figure 1
Figure 2
Figure 3
Figure 4
Figure 5
Figure 6
Figure 7
Figure 8
This is a list of supplementary files associated with this preprint. Click to download.
- GraphicalabstractimageJouranlofnanobiotechnology.png
Scheme 1 Schematic illustration of the lactate exhaustion process of PLNPCu nanosystem through extracellular lactate active-adsorption and establishment of the intracellular lactate treatment plant.
- scheme2.png
Scheme 2 Schematic illustration of the PLNPCu nanofactory closed-loop for lactate consumption and conversion.
- SupportingInformationJournalofnanobiotechnology.docx
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