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Research Article
Hoda Mahmoud
Alexandria University
Corresponding Author
Labiba El-Khordagui
Alexandria University
Corresponding Author
Ahmed Hussein
Alexandria University
Corresponding Author
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This work is licensed under a CC BY 4.0 License. Read Full License
Lactobacillus acidophilus ghosts (LAGs) with the unique safety of a probiotic, inherent tropism for colon cells and multiple bioactivities offer great promise as drug carrier for colon targeting. We report herein on a novel bioinspired drug delivery system against colorectal cancer (CRC) cells based on LAGs functionalized with prodigiosin (PG), a proapoptotic bacterial metabolite. LAGs were prepared by a chemical method and highly purified by density gradient centrifugation. Multiple microscopic and staining techniques characterized LAGs by a relatively small size, size uniformity, a relatively large internal volume devoid of cytoplasmic and genetic materials and an intact negatively charged envelop. PG was highly bound to LAGs cell wall, generating a physiologically stable bioactive entity (PG-LAGs) active against HCT116 CRC cells at the cellular and molecular levels. Cell viability data underlined cytotoxicity of PG and LAGs and LAGs-induced enhancement of PG selectivity for HCT116 cells. Combination and Dose reduction indices anticipating dose reduction of PG and LAGs. Molecularly, PG-LAGs significantly modulated the expression of apoptosis-related biomarkers, caspase 3, P53 and BCL2, in favor of cytotoxicity against HCT116 cells relative to PG and 5-fluorouracil. Accordingly, LAGs offer promise as novel drug carrier for targeted colon delivery and PG-LAGs may bring therapeutic benefits in colorectal carcinoma.
Keywords
Lactobacillus acidophilus ghosts, drug delivery system, colorectal cancer, prodigiosin
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No competing interests reported.
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This preprint is under consideration at Scientific Reports. 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
Hoda Mahmoud
Alexandria University
Corresponding Author
Labiba El-Khordagui
Alexandria University
Corresponding Author
Ahmed Hussein
Alexandria University
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: Under Review
Version 1
Posted 23 Mar, 2021
No community comments so far
Reviewers invited
Invitations sent on 13 Apr, 2021
Editor assigned
On 12 Apr, 2021
Editor invited
On 22 Mar, 2021
Submission checks complete
On 22 Mar, 2021
First submitted
On 21 Mar, 2021
Metrics
Comments: 0
PDF Downloads: ...
HTML Views: ...
License:
This work is licensed under a CC BY 4.0 License. Read Full License
Lactobacillus acidophilus ghosts (LAGs) with the unique safety of a probiotic, inherent tropism for colon cells and multiple bioactivities offer great promise as drug carrier for colon targeting. We report herein on a novel bioinspired drug delivery system against colorectal cancer (CRC) cells based on LAGs functionalized with prodigiosin (PG), a proapoptotic bacterial metabolite. LAGs were prepared by a chemical method and highly purified by density gradient centrifugation. Multiple microscopic and staining techniques characterized LAGs by a relatively small size, size uniformity, a relatively large internal volume devoid of cytoplasmic and genetic materials and an intact negatively charged envelop. PG was highly bound to LAGs cell wall, generating a physiologically stable bioactive entity (PG-LAGs) active against HCT116 CRC cells at the cellular and molecular levels. Cell viability data underlined cytotoxicity of PG and LAGs and LAGs-induced enhancement of PG selectivity for HCT116 cells. Combination and Dose reduction indices anticipating dose reduction of PG and LAGs. Molecularly, PG-LAGs significantly modulated the expression of apoptosis-related biomarkers, caspase 3, P53 and BCL2, in favor of cytotoxicity against HCT116 cells relative to PG and 5-fluorouracil. Accordingly, LAGs offer promise as novel drug carrier for targeted colon delivery and PG-LAGs may bring therapeutic benefits in colorectal carcinoma.
Figure 1
Figure 2
Figure 3
Figure 4
Figure 5
Figure 6
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