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Research Article
Wantao Chen
Shanghai 9th Peoples Hospital Affiliated to Shanghai Jiaotong University School of Medicine
Corresponding Author
ORCiD: https://orcid.org/0000-0002-9307-162X
License:
This work is licensed under a CC BY 4.0 License. Read Full License
Synergistic chemo-photodynamic therapy has attracted increasing attention in the field of cancer treatment. Herein, a pH cascade-responsive micellar nanoplatform with nucleus-targeted ability was fabricated, which could implement effective synergistic chemo-photodynamic cancer treatment. In this micellar nanoplatform, 5-(4-carboxyphenyl)-10,15,20-triphenylporphyrin (Por), a photodynamic therapy (PDT) agent, was utilized to carry the novel anticancer drug GNA002 to construct a hydrophobic core, and cyclic RGD peptide (cRGD)-modified polyethylene glycol (PEG) (cRGD-PEG) connected the cell-penetrating peptide hexaarginine (R6) through a pH-responsive hydrazone bond (cRGD-PEG-N=CH-R6) to serve as a hydrophilic shell for increasing blood circulation time. After passively accumulating in tumor sites, the self-assembled GNA002-loaded nanoparticles were actively internalized into cancer cells via cRGD ligands. Once phagocytosed by lysosomes, the acidity-triggered detachment of the cRGD-PEG shell led to the formation of R6-coated secondary nanoparticles and subsequent R6-mediated nucleus-targeted drug delivery. Combined with GNA002-induced nucleus-specific chemotherapy, reactive oxygen species produced by Por under 532-nm laser irradiation achieved a potent synergistic chemo-photodynamic cancer treatment. Moreover, our in vitro and in vivo anticancer investigations proved this ideal multifunctional nanoplatform showed a high cancer-suppression efficacy and could be a promising candidate for synergistic anticancer therapy.
Keywords
Multifunctional nanoplatform, pH-responsive amphiphilic polymer, Nuclear targeting, Drug delivery, Synergistic anticancer therapy
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- Scheme1.tif
Schematic illustration of a pH cascade-responsive nuclei-targeted nanoplatform for synergistic chemo-photodynamic therapy.
- Supplementarymaterial.docx
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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 Article
Wantao Chen
Shanghai 9th Peoples Hospital Affiliated to Shanghai Jiaotong University School of Medicine
Corresponding Author
ORCiD: https://orcid.org/0000-0002-9307-162X
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 15 Mar, 2021
No community comments so far
Editorial decision: Major revision
On 17 Mar, 2021
Review #1 received
Received 10 Mar, 2021
Review #2 received
Received 10 Mar, 2021
Reviewer #3 agreed
On 02 Mar, 2021
Editor invited
On 01 Mar, 2021
Editor assigned
On 01 Mar, 2021
Review #? received
Received 01 Mar, 2021
Reviewers invited
Invitations sent on 01 Mar, 2021
Reviewer #2 agreed
On 01 Mar, 2021
Reviewer #1 agreed
On 01 Mar, 2021
Submission checks complete
On 01 Mar, 2021
First submitted
On 28 Feb, 2021
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
Synergistic chemo-photodynamic therapy has attracted increasing attention in the field of cancer treatment. Herein, a pH cascade-responsive micellar nanoplatform with nucleus-targeted ability was fabricated, which could implement effective synergistic chemo-photodynamic cancer treatment. In this micellar nanoplatform, 5-(4-carboxyphenyl)-10,15,20-triphenylporphyrin (Por), a photodynamic therapy (PDT) agent, was utilized to carry the novel anticancer drug GNA002 to construct a hydrophobic core, and cyclic RGD peptide (cRGD)-modified polyethylene glycol (PEG) (cRGD-PEG) connected the cell-penetrating peptide hexaarginine (R6) through a pH-responsive hydrazone bond (cRGD-PEG-N=CH-R6) to serve as a hydrophilic shell for increasing blood circulation time. After passively accumulating in tumor sites, the self-assembled GNA002-loaded nanoparticles were actively internalized into cancer cells via cRGD ligands. Once phagocytosed by lysosomes, the acidity-triggered detachment of the cRGD-PEG shell led to the formation of R6-coated secondary nanoparticles and subsequent R6-mediated nucleus-targeted drug delivery. Combined with GNA002-induced nucleus-specific chemotherapy, reactive oxygen species produced by Por under 532-nm laser irradiation achieved a potent synergistic chemo-photodynamic cancer treatment. Moreover, our in vitro and in vivo anticancer investigations proved this ideal multifunctional nanoplatform showed a high cancer-suppression efficacy and could be a promising candidate for synergistic anticancer therapy.
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