Bioengineered and biohybrid bacteria-based systems for drug delivery

Hosseinidoust, Zeinab; Mostaghaci, Babak; Yaşa, Öncay; Park, Byung-Wook; Singh, Ajay Vikram; Sitti, Metin

doi:10.1016/j.addr.2016.09.007

Cited by 282 publications

(230 citation statements)

References 255 publications

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“…As the applications of metabolic engineering expand beyond traditional chemical production, tight control of output in response to the external environment will be necessary. Cells are already being engineered to specifically deliver drugs to tumors (Forbes 2010, Din et al 2016, Hosseinidoust et al 2016) and to produce different drugs based on what is needed in low-resource settings (Choi et al 2014, Perez-Pinera et al 2016). For both of these applications, it is necessary that cells produce the desired compound only in the desired condition—specificity of response based on environment is critical.…”

Section: Discussionmentioning

confidence: 99%

Precise control of lycopene production to enable a fast-responding, minimal-equipment biosensor

McNerney

Styczynski

2017

Metabolic Engineering

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Pigmented metabolites have great potential for use in biosensors that target low-resource areas, since sensor output can be interpreted without any equipment. However, full repression of pigment production when undesired is challenging, as even small amounts of enzyme can catalyze the production of large, visible amounts of pigment. The red pigment lycopene could be particularly useful because of its position in the multi-pigment carotenoid pathway, but commonly used inducible promoter systems cannot repress lycopene production. In this paper, we designed a system that could fully repress lycopene production in the absence of an inducer and produce visible lycopene within two hours of induction. We engineered Lac, Ara, and T7 systems to be up to 10 times more repressible, but these improved systems could still not fully repress lycopene. Translational modifications proved much more effective in controlling lycopene. By decreasing the strength of the ribosomal binding sites on the crtEBI genes, we enabled full repression of lycopene and production of visible lycopene in 3–4 hours of induction. Finally, we added the mevalonate pathway enzymes to increase the rate of lycopene production upon induction and demonstrated that supplementation of metabolic precursors could decrease the time to coloration to about 1.5 hours. In total, this represents over an order of magnitude reduction in response time compared to the previously reported strategy. The approaches used here demonstrate the disconnect between fluorescent and metabolite reporters, help enable the use of lycopene as a reporter, and are likely generalizable to other systems that require precise control of metabolite production.

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Section: Discussionmentioning

confidence: 99%

Precise control of lycopene production to enable a fast-responding, minimal-equipment biosensor

McNerney

Styczynski

2017

Metabolic Engineering

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“…Bacteria can also be genetically manipulated to produce targeting anticancer drugs to meet clinical needs 3,7. Additionally, bacteria are convenient to be chemically modified because of abundant chemical groups presenting on their surface 1,8. Given these advantages, versatile bacteria‐based tumor therapeutic platforms are promising to tackle significant challenges in tumor therapy 5,9–12…”

Section: Introductionmentioning

confidence: 99%

Self‐Mineralized Photothermal Bacteria Hybridizing with Mitochondria‐Targeted Metal–Organic Frameworks for Augmenting Photothermal Tumor Therapy

Chen

Liu

Fan

et al. 2020

Adv Funct Materials

141

106

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A photothermal bacterium (PTB) is reported for tumor‐targeted photothermal therapy (PTT) by using facultative anaerobic bacterium Shewanella oneidensis MR‐1 (S. oneidensis MR‐1) to biomineralize palladium nanoparticles (Pd NPs) on its surface without affecting bacterial activity. It is found that PTB possesses superior photothermal property in near infrared (NIR) regions, as well as preferential tumor‐targeting capacity. Zeolitic imidazole frameworks‐90 (ZIF‐90) encapsulating photosensitizer methylene blue (MB) are hybridized on the surface of living PTB to further enhance PTT efficacy. MB‐encapsulated ZIF‐90 (ZIF‐90/MB) can selectively release MB at mitochondria and cause mitochondrial dysfunction by producing singlet oxygen (1O2) under light illumination. Mitochondrial dysfunction further contributes to adenosine triphosphate (ATP) synthesis inhibition and heat shock proteins (HSPs) down‐regulated expression. The PTB‐based therapeutic platform of PTB@ZIF‐90/MB demonstrated here will find great potential to overcome the challenges of tumor targeting and tumor heat tolerance in PTT.

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“…Unlike other types of catalytic micromotors, biohybrid motors are powered by natural, nontoxic fuel sources found in biological media and operate by converting chemical energy into work . Due to the biocompatibility of their power source, biohybrid microsystems have the potential to operate in in vivo environments for biomedical drug and cargo delivery and micromanipulation of cell tissue . The miniaturized biohybrid motors aim to achieve what macroscale medical tools currently perform, but at the micrometer scale, making them less invasive and capable of functioning in smaller spaces.…”

Section: Introductionmentioning

confidence: 99%

Biohybrid Microtube Swimmers Driven by Single Captured Bacteria

Stanton

Park

Miguel-López

et al. 2017

Small

Self Cite

138

115

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Bacteria biohybrids employ the motility and power of swimming bacteria to carry and maneuver microscale particles. They have the potential to perform microdrug and cargo delivery in vivo, but have been limited by poor design, reduced swimming capabilities, and impeded functionality. To address these challenge, motile Escherichia coli are captured inside electropolymerized microtubes, exhibiting the first report of a bacteria microswimmer that does not utilize a spherical particle chassis. Single bacterium becomes partially trapped within the tube and becomes a bioengine to push the microtube though biological media. Microtubes are modified with “smart” material properties for motion control, including a bacteria‐attractant polydopamine inner layer, addition of magnetic components for external guidance, and a biochemical kill trigger to cease bacterium swimming on demand. Swimming dynamics of the bacteria biohybrid are quantified by comparing “length of protrusion” of bacteria from the microtubes with respect to changes in angular autocorrelation and swimmer mean squared displacement. The multifunctional microtubular swimmers present a new generation of biocompatible micromotors toward future microbiorobots and minimally invasive medical applications.

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Bioengineered and biohybrid bacteria-based systems for drug delivery

Cited by 282 publications

References 255 publications

Precise control of lycopene production to enable a fast-responding, minimal-equipment biosensor

Precise control of lycopene production to enable a fast-responding, minimal-equipment biosensor

Self‐Mineralized Photothermal Bacteria Hybridizing with Mitochondria‐Targeted Metal–Organic Frameworks for Augmenting Photothermal Tumor Therapy

Biohybrid Microtube Swimmers Driven by Single Captured Bacteria

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