Doxorubicin-conjugated Escherichia coli Nissle 1917 swimmers to achieve tumor targeting and responsive drug release

Xie, Songzhi; Zhao, Long; Song, Xiaojie; Tang, Maosheng; Mo, Chuanfei; Li, Xiaohong

doi:10.1016/j.jconrel.2017.10.041

Cited by 106 publications

(78 citation statements)

References 44 publications

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“…These results agree with other data reported by other research groups which indicate that the presence of Doxorubicin does not affect significantly neither growth nor viability of bacteria. [ 25 ]…”

Section: Resultsmentioning

confidence: 99%

“…[ 22 ] Moreover, these tiny microorganisms are able to move toward gradients in response to small changes in internal stimulus (specific chemicals, temperature, or pH variations), or guided by external stimulus (magnetic field). [ 23–27 ] Thus, anaerobes bacteria are able to colonize hypoxic regions into tumoral tissues reaching inner zones of the malignancy, as has been studied in vitro and in vivo. [ 28–30 ] Herein, we report the use of Escherichia coli ( E. coli) as model of facultative anaerobic bacteria for the transportation of mesoporous silica nanoparticles (MSN) loaded with a potent cytotoxic compound, doxorubicin (Dox).…”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Bacteria as Nanoparticles Carrier for Enhancing Penetration in a Tumoral Matrix Model

Moreno

Álvarez

Izquierdo‐Barba

et al. 2020

Adv Materials Inter

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One of the major concerns in the application of nanocarriers in oncology is their scarce penetration capacity in tumoral tissues. Living organisms (cells and bacteria) present the capacity to navigate autonomously following chemical gradients being able to penetrate deeply into dense tissues. Currently, the possibility to employ these organisms for the transportation of therapeutic agents or nanocarriers has received huge attention. Herein, a new approach to deliver drug‐loaded nanoparticles achieving high penetration in tumoral matrices is presented. Escherichia coli bacteria wall is decorated with azide groups, whereas alkyne‐strained groups are incorporated on the surface of mesoporous silica nanoparticles loaded with a potent cytotoxic compound, doxorubicin. Both functional groups form stable triazole bonds by click‐type reaction allowing the covalent grafting of nanoparticles on living bacteria. Both motility and penetration capacity are evaluated in a 3D tumoral matrix model composed by a dense collagen extracellular matrix containing human fibrosarcome cells. The results confirm that bacteria are able to transport the nanoparticles crossing a thick collagen layer being able to destroy almost 80% of the tumoral cells located underneath. These findings envision a powerful strategy in cancer treatment by allowing a homogeneous distribution of therapeutic agents in the malignancy.

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Section: Resultsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Bacteria as Nanoparticles Carrier for Enhancing Penetration in a Tumoral Matrix Model

Moreno

Álvarez

Izquierdo‐Barba

et al. 2020

Adv Materials Inter

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“…Another important aspect of biohybrids is their biological safety. For example, despite the claims of using bacterial biohybrid microswimmers for human health applications, such as drug delivery (reviewed in reference [30]), the references to the investigation of probiotic bacteria [31] or microorganisms with granted Qualified Presumption of Safety (QPS, from the European Food Safety Authority (EFSA)) [32] or Generally Recognized as Safe (GRAS, from the US Food and Drug Administration (FDA)) status as biohybrid carriers, are scarce [3,33,34]. Interestingly, most probiotic bacteria (e.g., Lactobacilli and Bifidobacteria) [31] and bacteria with QPS status [35] are Gram-positives.…”

Section: Figurementioning

confidence: 99%

Genetically Engineered Bacterial Biohybrid Microswimmers for Sensing Applications

Sun

Loderer

Revilla-Guarinos

2019

Sensors

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Bacterial biohybrid microswimmers aim at exploiting the inherent motion capabilities of bacteria (carriers) to transport objects (cargoes) at the microscale. One of the most desired properties of microswimmers is their ability to communicate with their immediate environment by processing the information and producing a useful response. Indeed, bacteria are naturally equipped with such communication skills. Hereby, two-component systems (TCSs) represent the key signal transducing machinery and enable bacteria to sense and respond to a variety of stimuli. We engineered a natural microswimmer based on the Gram-positive model bacterium Bacillus subtilis for the development of biohybrids with sensing abilities. B. subtilis naturally adhered to silica particles, giving rise to different motile biohybrids systems with variable ratios of carrier(s)-to-cargo(es). Genetically engineered TCS pathways allowed us to couple the binding to the inert particles with signaling the presence of antibiotics in their surroundings. Activation of the antibiotic-induced TCSs resulted in fluorescent bacterial carriers as a response readout. We demonstrate that the genetically engineered TCS-mediated signaling capabilities of B. subtilis allow for the custom design of bacterial hybrid microswimmers able to sense and signal the presence of target molecules in the environment. The generally recognized as safe (GRAS) status of B. subtilis makes it a promising candidate for human-related applications of these novel biohybrids.

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“…Potential applications such as microsurgery [ 4 ], tumor imaging and ablation [ 5 , 6 ], tissue biopsies [ 7 ], targeted drug delivery [ 8 , 9 , 10 ], cell delivery [ 11 , 12 ], and gene silencing [ 13 , 14 ] have recently been explored, with demonstrations of microrobot viability in both in vitro and in vivo conditions. Polymer nanoplatforms have been shown to release chemicals to different stimuli such as presence of certain enzymes, pH changes, temperature differences, ultrasound, etc.…”

Section: Introductionmentioning

confidence: 99%

A Tumbling Magnetic Microrobot System for Biomedical Applications

Niedert

Adam

et al. 2020

Micromachines

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A microrobot system comprising an untethered tumbling magnetic microrobot, a two-degree-of-freedom rotating permanent magnet, and an ultrasound imaging system has been developed for in vitro and in vivo biomedical applications. The microrobot tumbles end-over-end in a net forward motion due to applied magnetic torque from the rotating magnet. By turning the rotational axis of the magnet, two-dimensional directional control is possible and the microrobot was steered along various trajectories, including a circular path and P-shaped path. The microrobot is capable of moving over the unstructured terrain within a murine colon in in vitro, in situ, and in vivo conditions, as well as a porcine colon in ex vivo conditions. High-frequency ultrasound imaging allows for real-time determination of the microrobot’s position while it is optically occluded by animal tissue. When coated with a fluorescein payload, the microrobot was shown to release the majority of the payload over a 1-h time period in phosphate-buffered saline. Cytotoxicity tests demonstrated that the microrobot’s constituent materials, SU-8 and polydimethylsiloxane (PDMS), did not show a statistically significant difference in toxicity to murine fibroblasts from the negative control, even when the materials were doped with magnetic neodymium microparticles. The microrobot system’s capabilities make it promising for targeted drug delivery and other in vivo biomedical applications.

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Doxorubicin-conjugated Escherichia coli Nissle 1917 swimmers to achieve tumor targeting and responsive drug release

Cited by 106 publications

References 44 publications

Bacteria as Nanoparticles Carrier for Enhancing Penetration in a Tumoral Matrix Model

Bacteria as Nanoparticles Carrier for Enhancing Penetration in a Tumoral Matrix Model

Genetically Engineered Bacterial Biohybrid Microswimmers for Sensing Applications

A Tumbling Magnetic Microrobot System for Biomedical Applications

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