Robust and Repeatable Biofabrication of Bacteria‐Mediated Drug Delivery Systems: Effect of Conjugation Chemistry, Assembly Process Parameters, and Nanoparticle Size
Bacteria‐mediated drug delivery systems comprising nanotherapeutics conjugated onto bacteria synergistically augment the efficacy of both therapeutic modalities in cancer therapy. Nanocarriers preserve therapeutics’ bioavailability and reduce systemic toxicity, while bacteria selectively colonize th...
| Main Authors: | , , , , |
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| Format: | Article |
| Language: | English |
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Wiley
2022-03-01
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| Series: | Advanced Intelligent Systems |
| Subjects: | |
| Online Access: | https://doi.org/10.1002/aisy.202100135 |
| _version_ | 1819157832149237760 |
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| author | Ying Zhan Austin Fergusson Lacey R. McNally Richey M. Davis Bahareh Behkam |
| author_facet | Ying Zhan Austin Fergusson Lacey R. McNally Richey M. Davis Bahareh Behkam |
| author_sort | Ying Zhan |
| collection | DOAJ |
| description | Bacteria‐mediated drug delivery systems comprising nanotherapeutics conjugated onto bacteria synergistically augment the efficacy of both therapeutic modalities in cancer therapy. Nanocarriers preserve therapeutics’ bioavailability and reduce systemic toxicity, while bacteria selectively colonize the cancerous tissue, impart intrinsic and immune‐mediated antitumor effects, and propel nanotherapeutics interstitially. The optimal bacteria–nanoparticle (NP) conjugates will carry the maximal NP load with minimal motility speed hindrance for effective interstitial distribution. Furthermore, a well‐defined and repeatable NP attachment density distribution is crucial to determining these biohybrid systems’ efficacious dosage and robust performance. Herein, our nanoscale bacteria‐enabled autonomous delivery system (NanoBEADS) platform is utilized to investigate the effects of assembly process parameters of mixing method, volume, and duration on NP attachment density and repeatability. The effect of linkage chemistry and NP size on NP attachment density, viability, growth rate, and motility of NanoBEADS is also evaluated. It is shown that the linkage chemistry impacts NP attachment density while the self‐assembly process parameters affect the repeatability and, to a lesser extent, attachment density. Lastly, the attachment density affects NanoBEADS’ growth rate and motility in an NP size‐dependent manner. These findings will contribute to the development of scalable and repeatable bacteria–NP biohybrids for applications in drug delivery and beyond. An interactive preprint version of the article can be found here: https://www.authorea.com/doi/full/10.22541/au.163100509.93917936. |
| first_indexed | 2024-12-22T16:15:01Z |
| format | Article |
| id | doaj.art-021263c194fd45f38144898bdaabca00 |
| institution | Directory Open Access Journal |
| issn | 2640-4567 |
| language | English |
| last_indexed | 2024-12-22T16:15:01Z |
| publishDate | 2022-03-01 |
| publisher | Wiley |
| record_format | Article |
| series | Advanced Intelligent Systems |
| spelling | doaj.art-021263c194fd45f38144898bdaabca002022-12-21T18:20:22ZengWileyAdvanced Intelligent Systems2640-45672022-03-0143n/an/a10.1002/aisy.202100135Robust and Repeatable Biofabrication of Bacteria‐Mediated Drug Delivery Systems: Effect of Conjugation Chemistry, Assembly Process Parameters, and Nanoparticle SizeYing Zhan0Austin Fergusson1Lacey R. McNally2Richey M. Davis3Bahareh Behkam4Department of Mechanical Engineering Virginia Tech Blacksburg VA 24061 USAGraduate Program in Translational Biology, Medicine, and Health Virginia Tech Blacksburg VA 24061 USAStephenson School of Biomedical Engineering University of Oklahoma Norman OK 73019 USADepartment of Chemical Engineering Macromolecules Innovation Institute Virginia Tech Blacksburg VA 24061 USADepartment of Mechanical Engineering Virginia Tech Blacksburg VA 24061 USABacteria‐mediated drug delivery systems comprising nanotherapeutics conjugated onto bacteria synergistically augment the efficacy of both therapeutic modalities in cancer therapy. Nanocarriers preserve therapeutics’ bioavailability and reduce systemic toxicity, while bacteria selectively colonize the cancerous tissue, impart intrinsic and immune‐mediated antitumor effects, and propel nanotherapeutics interstitially. The optimal bacteria–nanoparticle (NP) conjugates will carry the maximal NP load with minimal motility speed hindrance for effective interstitial distribution. Furthermore, a well‐defined and repeatable NP attachment density distribution is crucial to determining these biohybrid systems’ efficacious dosage and robust performance. Herein, our nanoscale bacteria‐enabled autonomous delivery system (NanoBEADS) platform is utilized to investigate the effects of assembly process parameters of mixing method, volume, and duration on NP attachment density and repeatability. The effect of linkage chemistry and NP size on NP attachment density, viability, growth rate, and motility of NanoBEADS is also evaluated. It is shown that the linkage chemistry impacts NP attachment density while the self‐assembly process parameters affect the repeatability and, to a lesser extent, attachment density. Lastly, the attachment density affects NanoBEADS’ growth rate and motility in an NP size‐dependent manner. These findings will contribute to the development of scalable and repeatable bacteria–NP biohybrids for applications in drug delivery and beyond. An interactive preprint version of the article can be found here: https://www.authorea.com/doi/full/10.22541/au.163100509.93917936.https://doi.org/10.1002/aisy.202100135bacteria-based cancer therapybiohybrid robotscell-mediated drug delivery systemsSalmonella enterica serovar Typhimuriumtumor-targeting bacteria |
| spellingShingle | Ying Zhan Austin Fergusson Lacey R. McNally Richey M. Davis Bahareh Behkam Robust and Repeatable Biofabrication of Bacteria‐Mediated Drug Delivery Systems: Effect of Conjugation Chemistry, Assembly Process Parameters, and Nanoparticle Size Advanced Intelligent Systems bacteria-based cancer therapy biohybrid robots cell-mediated drug delivery systems Salmonella enterica serovar Typhimurium tumor-targeting bacteria |
| title | Robust and Repeatable Biofabrication of Bacteria‐Mediated Drug Delivery Systems: Effect of Conjugation Chemistry, Assembly Process Parameters, and Nanoparticle Size |
| title_full | Robust and Repeatable Biofabrication of Bacteria‐Mediated Drug Delivery Systems: Effect of Conjugation Chemistry, Assembly Process Parameters, and Nanoparticle Size |
| title_fullStr | Robust and Repeatable Biofabrication of Bacteria‐Mediated Drug Delivery Systems: Effect of Conjugation Chemistry, Assembly Process Parameters, and Nanoparticle Size |
| title_full_unstemmed | Robust and Repeatable Biofabrication of Bacteria‐Mediated Drug Delivery Systems: Effect of Conjugation Chemistry, Assembly Process Parameters, and Nanoparticle Size |
| title_short | Robust and Repeatable Biofabrication of Bacteria‐Mediated Drug Delivery Systems: Effect of Conjugation Chemistry, Assembly Process Parameters, and Nanoparticle Size |
| title_sort | robust and repeatable biofabrication of bacteria mediated drug delivery systems effect of conjugation chemistry assembly process parameters and nanoparticle size |
| topic | bacteria-based cancer therapy biohybrid robots cell-mediated drug delivery systems Salmonella enterica serovar Typhimurium tumor-targeting bacteria |
| url | https://doi.org/10.1002/aisy.202100135 |
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