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Research article
Jun Bao
Corresponding Author
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Background: Tumor recurrence and metastasis occur at a high rate in patients with colon cancer. Identification of effective strategies for the treatment of colon cancer is critical. Recently, poly (lactic-co-glycolic acid) (PLGA) has been shown to have potential as a broad therapeutic drug delivery system. We designed a dual-loaded nanoparticle drug delivery system to overcome the limitations of chemotherapeutic drugs used to treat colon cancer. Methods: We developed epidermal growth factor (EGF) functionalized PLGA nanoparticles (NPs) co-loaded with 5-fluorouracil (5Fu) and perfluorocarbon (PFC) ([email protected]/PFC) for targeted treatment of colon cancer. CCK-8 assay, Hoechst33342 staining and flow cytometry were performed to investigate the functions of [email protected]/PFC NPs in SW620 cells. Beside, animal experiment, histological analysis and immunofluorescence staining were adopted to further confirm the role of [email protected]/PFC NPs in vivo. Results: The findings showed that [email protected] /PFC NPs had an average size 200 nm and a 5Fu-loading efficiency of 7.29%. Furthermore, in vitro release was pH-sensitive. Targeted [email protected]/PFC NPs exhibited higher cellular uptake than non-targeted NPs into colon cancer cells. In addition, [email protected]/PFC NPs suppressed cell viability and induced apoptosis in SW620 cells to a greater extent than non-targeted NPs. In tumor xenografted mice, [email protected]/PFC NPs suppressed tumor growth more effectively than 5Fu, [email protected] or [email protected]/PFC NPs. Histopathological analysis further demonstrated that EGF-targeted NPs inhibited tumor growth to a greater extent than non-targeted or non-NP treatments. The improved therapeutic outcomes observed in this study were due to relief of tumor hypoxia by transport of oxygen by PFC to the tumors. Conclusion: We constructed a biocompatible nanodrug delivery system based on functionalized nanoparticles that provided a novel strategy for selective delivery of chemotherapy drugs to tumors.
Keywords
PLGA nanoparticles, 5-fluorouracil, perfluorocarbon, EGF, hypoxia, colon cancer
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CURRENT STATUS: Published
View the published article at BMC Cancer.
Version 4
Posted 31 Mar, 2020
No community comments so far
Editorial decision: Accept
On 27 Mar, 2020
Editor assigned
On 26 Mar, 2020
Submission checks complete
On 25 Mar, 2020
Editor invited
On 25 Mar, 2020
No comments provided
Editorial decision: Minor revision
On 23 Mar, 2020
Review #2 received
Received 18 Mar, 2020
Review #1 received
Received 14 Mar, 2020
Reviewer #2 agreed
On 03 Mar, 2020
Editor assigned
On 26 Feb, 2020
Reviewers invited
Invitations sent on 26 Feb, 2020
Reviewer #1 agreed
On 26 Feb, 2020
Submission checks complete
On 25 Feb, 2020
Editor invited
On 25 Feb, 2020
No comments provided
Editorial decision: Minor revision
On 11 Jan, 2020
Review #1 received
Received 31 Dec, 2019
Reviewer #2 agreed
On 20 Dec, 2019
Review #2 received
Received 20 Dec, 2019
Reviewers invited
Invitations sent on 16 Dec, 2019
Reviewer #1 agreed
On 16 Dec, 2019
Editor assigned
On 13 Dec, 2019
Submission checks complete
On 12 Dec, 2019
Editor invited
On 12 Dec, 2019
No comments provided
Editorial decision: Minor revision
On 09 Dec, 2019
Review #4 received
Received 06 Dec, 2019
Review #2 received
Received 30 Nov, 2019
Review #1 received
Received 25 Nov, 2019
Reviewer #5 agreed
On 23 Nov, 2019
Reviewer #4 agreed
On 22 Nov, 2019
Review #3 received
Received 22 Nov, 2019
Reviewer #3 agreed
On 22 Nov, 2019
Reviewer #2 agreed
On 19 Nov, 2019
Reviewer #1 agreed
On 15 Nov, 2019
Submission checks complete
On 11 Nov, 2019
Editor invited
On 11 Nov, 2019
Editor assigned
On 11 Nov, 2019
Reviewers invited
Invitations sent on 11 Nov, 2019
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A new preprint design is coming!
We have improved readability, clarity, accessibility, and opportunities for engagement.
See the published version of this preprint at BMC Cancer.
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.
Learn more about In Review
Research article
Jun Bao
Corresponding Author
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
View the published article at BMC Cancer.
Version 4
Posted 31 Mar, 2020
No community comments so far
Editorial decision: Accept
On 27 Mar, 2020
Editor assigned
On 26 Mar, 2020
Submission checks complete
On 25 Mar, 2020
Editor invited
On 25 Mar, 2020
No comments provided
Editorial decision: Minor revision
On 23 Mar, 2020
Review #2 received
Received 18 Mar, 2020
Review #1 received
Received 14 Mar, 2020
Reviewer #2 agreed
On 03 Mar, 2020
Editor assigned
On 26 Feb, 2020
Reviewers invited
Invitations sent on 26 Feb, 2020
Reviewer #1 agreed
On 26 Feb, 2020
Submission checks complete
On 25 Feb, 2020
Editor invited
On 25 Feb, 2020
No comments provided
Editorial decision: Minor revision
On 11 Jan, 2020
Review #1 received
Received 31 Dec, 2019
Reviewer #2 agreed
On 20 Dec, 2019
Review #2 received
Received 20 Dec, 2019
Reviewers invited
Invitations sent on 16 Dec, 2019
Reviewer #1 agreed
On 16 Dec, 2019
Editor assigned
On 13 Dec, 2019
Submission checks complete
On 12 Dec, 2019
Editor invited
On 12 Dec, 2019
No comments provided
Editorial decision: Minor revision
On 09 Dec, 2019
Review #4 received
Received 06 Dec, 2019
Review #2 received
Received 30 Nov, 2019
Review #1 received
Received 25 Nov, 2019
Reviewer #5 agreed
On 23 Nov, 2019
Reviewer #4 agreed
On 22 Nov, 2019
Review #3 received
Received 22 Nov, 2019
Reviewer #3 agreed
On 22 Nov, 2019
Reviewer #2 agreed
On 19 Nov, 2019
Reviewer #1 agreed
On 15 Nov, 2019
Submission checks complete
On 11 Nov, 2019
Editor invited
On 11 Nov, 2019
Editor assigned
On 11 Nov, 2019
Reviewers invited
Invitations sent on 11 Nov, 2019
Metrics
Comments: 0
PDF Downloads: ...
HTML Views: ...
License:
This work is licensed under a CC BY 4.0 License. Read Full License
View the published article at BMC Cancer.
Background: Tumor recurrence and metastasis occur at a high rate in patients with colon cancer. Identification of effective strategies for the treatment of colon cancer is critical. Recently, poly (lactic-co-glycolic acid) (PLGA) has been shown to have potential as a broad therapeutic drug delivery system. We designed a dual-loaded nanoparticle drug delivery system to overcome the limitations of chemotherapeutic drugs used to treat colon cancer. Methods: We developed epidermal growth factor (EGF) functionalized PLGA nanoparticles (NPs) co-loaded with 5-fluorouracil (5Fu) and perfluorocarbon (PFC) ([email protected]/PFC) for targeted treatment of colon cancer. CCK-8 assay, Hoechst33342 staining and flow cytometry were performed to investigate the functions of [email protected]/PFC NPs in SW620 cells. Beside, animal experiment, histological analysis and immunofluorescence staining were adopted to further confirm the role of [email protected]/PFC NPs in vivo. Results: The findings showed that [email protected] /PFC NPs had an average size 200 nm and a 5Fu-loading efficiency of 7.29%. Furthermore, in vitro release was pH-sensitive. Targeted [email protected]/PFC NPs exhibited higher cellular uptake than non-targeted NPs into colon cancer cells. In addition, [email protected]/PFC NPs suppressed cell viability and induced apoptosis in SW620 cells to a greater extent than non-targeted NPs. In tumor xenografted mice, [email protected]/PFC NPs suppressed tumor growth more effectively than 5Fu, [email protected] or [email protected]/PFC NPs. Histopathological analysis further demonstrated that EGF-targeted NPs inhibited tumor growth to a greater extent than non-targeted or non-NP treatments. The improved therapeutic outcomes observed in this study were due to relief of tumor hypoxia by transport of oxygen by PFC to the tumors. Conclusion: We constructed a biocompatible nanodrug delivery system based on functionalized nanoparticles that provided a novel strategy for selective delivery of chemotherapy drugs to tumors.
Figure 1
Figure 2
Figure 3
Figure 4
Figure 5
Figure 6
This is a list of supplementary files associated with this preprint. Click to download.
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