Macromolecules Innovation Institute (MII)

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Browsing Macromolecules Innovation Institute (MII) by Author "Behkam, Bahareh"

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    Nanoscale Bacteria‐Enabled Autonomous Drug Delivery System (NanoBEADS) Enhances Intratumoral Transport of Nanomedicine
    Suh, SeungBeum; Jo, Ami; Traore, Mahama Aziz; Zhan, Ying; Coutermarsh-Ott, Sheryl; Ringel-Scaia, Veronica M.; Allen, Irving C.; Davis, Richey M.; Behkam, Bahareh (Wiley, 2018-12-05)
    Cancer drug delivery remains a formidable challenge due to systemic toxicity and inadequate extravascular transport of nanotherapeutics to cells distal from blood vessels. It is hypothesized that, in absence of an external driving force, the Salmonella enterica serovar Typhimurium could be exploited for autonomous targeted delivery of nanotherapeutics to currently unreachable sites. To test the hypothesis, a nanoscale bacteria‐enabled autonomous drug delivery system (NanoBEADS) is developed in which the functional capabilities of the tumor‐targeting S. Typhimurium VNP20009 are interfaced with poly(lactic‐co‐glycolic acid) nanoparticles. The impact of nanoparticle conjugation is evaluated on NanoBEADS' invasion of cancer cells and intratumoral transport in 3D tumor spheroids in vitro, and biodistribution in a mammary tumor model in vivo. It is found that intercellular (between cells) self‐replication and translocation are the dominant mechanisms of bacteria intratumoral penetration and that nanoparticle conjugation does not impede bacteria's intratumoral transport performance. Through the development of new transport metrics, it is demonstrated that NanoBEADS enhance nanoparticle retention and distribution in solid tumors by up to a remarkable 100‐fold without requiring any externally applied driving force or control input. Such autonomous biohybrid systems could unlock a powerful new paradigm in cancer treatment by improving the therapeutic index of chemotherapeutic drugs and minimizing systemic side effects.
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    Robust and Repeatable Biofabrication of Bacteria-Mediated Drug Delivery Systems: Effect of Conjugation Chemistry, Assembly Process Parameters, and Nanoparticle Size
    Zhan, Ying; Fergusson, Austin D.; McNally, Lacey R.; Davis, Richey M.; Behkam, Bahareh (2021-11-19)
    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.