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Ruoning Wang
Nanjing University of Chinese Medicine
Corresponding Author
ORCiD: https://orcid.org/0000-0001-7466-9602
License:
This work is licensed under a CC BY 4.0 License. Read Full License
View the published article at Journal of Nanobiotechnology.
Background: The management of metastatic cancer remains a major challenge in cancer therapy worldwide. The targeted delivery of chemotherapeutic drugs through rationally designed formulations is one potential therapeutic option. Notably, excipient-free nanodispersions that are entirely composed of pharmaceutically active molecules have been evaluated as promising candidates for the next generation of drug formulations. Formulated from the self-assembly of drug molecules, these nanodispersions enable the safe and effective delivery of therapeutic drugs to local disease lesions. Here, we developed a novel and green approach for preparing nanoparticles via the self-assembly of rhein (RHE) and doxorubicin (DOX) molecules, named RHE/DOX nanoparticles (RD NPs); this assembly was associated with the interaction force and did not involve any organic solvents.
Results: According to molecular dynamics (MD) simulations, DOX molecules tend to assemble around RHE molecules through intermolecular forces. This intermolecular retention of DOX was further improved by the nanosizing effect of RD NPs. Compared to free DOX, RD NPs exerted a slightly stronger inhibitory effect on 4T1 cells in the scratch healing assay. As a dual drug-loaded nanoformulation, the efficacy of RD NPs against tumor cells in vitro was synergistically enhanced. Compared to free DOX, the combination of DOX and RHE in nanoparticles exerted a synergistic effect with a combination index (CI) value of 0.51 and showed a stronger ability to induce cell apoptosis. Furthermore, the RD NP treatment not only effectively suppressed primary tumor growth but also significantly inhibited tumor metastasis both in vitro and in vivo, with a better safety profile.
Conclusions: The generation of pure nanodrugs via a self-assembly approach might hold promise for the development of more efficient and novel excipient-free nanodispersions, particularly for two small molecular antitumor drugs that potentially exert synergistic antiproliferative effects on metastatic breast cancer.
Keywords
Metastatic cancer, Synergistic antiproliferative effect, Rhein (RHE) and doxorubicin (DOX), Excipient-free nanodispersions
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CURRENT STATUS: Published
Version 2
Posted 30 Jul, 2020
Published
On 26 Aug, 2020
No community comments so far
Editorial decision: Accept
On 15 Aug, 2020
Review #1 received
Received 31 Jul, 2020
Reviewers invited
Invitations sent on 26 Jul, 2020
Reviewer #1 agreed
On 26 Jul, 2020
Editor assigned
On 24 Jul, 2020
Submission checks complete
On 23 Jul, 2020
Editor invited
On 23 Jul, 2020
No comments provided
Editorial decision: Major revision
On 06 Jun, 2020
Review #1 received
Received 05 Jun, 2020
Review #2 received
Received 26 May, 2020
Review #3 received
Received 26 May, 2020
Reviewer #2 agreed
On 11 May, 2020
Reviewer #3 agreed
On 11 May, 2020
Reviewer #1 agreed
On 01 Apr, 2020
Reviewers invited
Invitations sent on 13 Mar, 2020
Editor invited
On 04 Mar, 2020
Editor assigned
On 04 Mar, 2020
First submitted
On 03 Mar, 2020
Submission checks complete
On 03 Mar, 2020
Metrics
Comments: 0
PDF Downloads: ...
HTML Views: ...
Subject Areas
Nanoscience
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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
Ruoning Wang
Nanjing University of Chinese Medicine
Corresponding Author
ORCiD: https://orcid.org/0000-0001-7466-9602
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 30 Jul, 2020
Published
On 26 Aug, 2020
No community comments so far
Editorial decision: Accept
On 15 Aug, 2020
Review #1 received
Received 31 Jul, 2020
Reviewers invited
Invitations sent on 26 Jul, 2020
Reviewer #1 agreed
On 26 Jul, 2020
Editor assigned
On 24 Jul, 2020
Submission checks complete
On 23 Jul, 2020
Editor invited
On 23 Jul, 2020
No comments provided
Editorial decision: Major revision
On 06 Jun, 2020
Review #1 received
Received 05 Jun, 2020
Review #2 received
Received 26 May, 2020
Review #3 received
Received 26 May, 2020
Reviewer #2 agreed
On 11 May, 2020
Reviewer #3 agreed
On 11 May, 2020
Reviewer #1 agreed
On 01 Apr, 2020
Reviewers invited
Invitations sent on 13 Mar, 2020
Editor invited
On 04 Mar, 2020
Editor assigned
On 04 Mar, 2020
First submitted
On 03 Mar, 2020
Submission checks complete
On 03 Mar, 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 article at Journal of Nanobiotechnology.
Background: The management of metastatic cancer remains a major challenge in cancer therapy worldwide. The targeted delivery of chemotherapeutic drugs through rationally designed formulations is one potential therapeutic option. Notably, excipient-free nanodispersions that are entirely composed of pharmaceutically active molecules have been evaluated as promising candidates for the next generation of drug formulations. Formulated from the self-assembly of drug molecules, these nanodispersions enable the safe and effective delivery of therapeutic drugs to local disease lesions. Here, we developed a novel and green approach for preparing nanoparticles via the self-assembly of rhein (RHE) and doxorubicin (DOX) molecules, named RHE/DOX nanoparticles (RD NPs); this assembly was associated with the interaction force and did not involve any organic solvents.
Results: According to molecular dynamics (MD) simulations, DOX molecules tend to assemble around RHE molecules through intermolecular forces. This intermolecular retention of DOX was further improved by the nanosizing effect of RD NPs. Compared to free DOX, RD NPs exerted a slightly stronger inhibitory effect on 4T1 cells in the scratch healing assay. As a dual drug-loaded nanoformulation, the efficacy of RD NPs against tumor cells in vitro was synergistically enhanced. Compared to free DOX, the combination of DOX and RHE in nanoparticles exerted a synergistic effect with a combination index (CI) value of 0.51 and showed a stronger ability to induce cell apoptosis. Furthermore, the RD NP treatment not only effectively suppressed primary tumor growth but also significantly inhibited tumor metastasis both in vitro and in vivo, with a better safety profile.
Conclusions: The generation of pure nanodrugs via a self-assembly approach might hold promise for the development of more efficient and novel excipient-free nanodispersions, particularly for two small molecular antitumor drugs that potentially exert synergistic antiproliferative effects on metastatic breast cancer.
Figure 1
Figure 2
Figure 3
Figure 4
Figure 5
Figure 6
Figure 7
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