Biology subjects

Gwisai, T.

Publications and source records attributed to Gwisai, T..

5 recordsLinked to original sources

bioRxiv2023

Engineering living immunotherapeutic agents for improved cancer treatment

Bacteria-based biohybrid agents are emerging as a promising strategy for cancer therapy due to their ability to actively target tumors, trigger localized inflammation and induce tumor regression. There has been growing interest in using bacteria that are responsive to external cues, such as magnetic fields, to facilitate the formation of robust colonies in tumor the achieve the threshold for clinical efficacy. Several studied have demonstrated the potential of innately magnetically responsive bacteria, known as magnetotactic bacteria (MTB), as steerable agents, however, their immunostimulatory properties and therapeutic effects are yet to be explored. Here, we characterize key properties of human immune cell responses and the behavior of the MTB strain Magnetospirillum magneticum AMB-1 in physiological environments. This work investigates the ability of MTB to maintain magnetic properties, viability in whole blood, cytokine production by macrophages, and the ability to increase uptake of cancer cell material by dendritic cells. This study also explores the use of MTB-liposome complexes for effective delivery of therapeutic payloads. Overall, this study establishes the potential of MTB as a versatile, combined drug delivery platform for immune-mediated cancer therapy.

bioengineering↗

bioRxiv2023

Spatially selective open loop control of magnetic microrobots for drug delivery

Rotating magnetic fields (RMFs), when used to actuate biomedical microrobots for targeted delivery to tumors, have been shown to enable them to overcome physiological barriers and promote their accumulation and penetration into tissue. Nevertheless, directly applying a RMF to a deeply situated target site also leads to off-target actuation in surrounding healthy tissue. Here, we investigate an open-loop control strategy for delivering torque density to diffuse distributions of microrobots at focal points by combining RMFs with magnetostatic gating fields. Taking magnetotactic bacteria (MTB) as a model biohybrid microrobotic system for torque-based actuation, we first use simulation to elucidate off-target torque suppression and find that resolution is set by the relative magnitude of the magnetostatic field and RMF. We study focal torque delivery in vitro, observing off-target suppression of translational velocity of MTB, convection-driven accumulation of companion nanoparticles, and tumor spheroid colonization. We then design, construct, and validate a mouse-scale torque-focusing apparatus incorporating a permanent magnet array, three-phase RMF coils, and offset coils to maneuver the focal point. Our control scheme enables the advantages of torque-based actuation to be combined with spatial targeting, and could be broadly applied to other microrobotic designs for improved drug delivery. One-Sentence SummaryCombining rotating magnetic fields with gating fields enables focused delivery of torque density to dispersed microrobots.

bioengineering↗

bioRxiv2022

Magnetic torque-driven living microrobots for enhanced tumor infiltration

Bacterial microrobots combining self-propulsion and magnetic guidance are increasingly recognized as promising drug delivery vehicles for targeted cancer therapy. Thus far, control strategies have either relied on poorly scalable magnetic field gradients or employed directing magnetic fields with propulsive forces limited by the bacterial motor. Here, we present a magnetic torque-driven actuation scheme based on rotating magnetic fields to wirelessly control Magnetospirillum magneticum AMB-1 bearing versatile liposomal cargo. We observed a 4-fold increase in conjugate translocation across a model of the vascular endothelium and found that the primary mechanism driving this increased transport is torque-driven surface exploration at the cell interface. Using spheroids as a 3D tumor model, fluorescently labeled bacteria colonized their core regions with up to 21-fold higher signal in samples exposed to rotating magnetic fields. In addition to enhanced transport, we demonstrated the suitability of this magnetic stimulus for simultaneous actuation and inductive detection of AMB-1. Finally, we demonstrated that RMF significantly enhances AMB-1 tumor accumulation in vivo following systemic intravenous administration in mice. Our findings suggest that scalable magnetic torque-driven control strategies can be leveraged advantageously with biohybrid microrobots. One-Sentence SummaryMagnetic torque-driven motion enhances infiltration of living microrobots across physiological barriers both in vitro and in vivo.

bioengineering↗

bioRxiv2020

Magnetospirillum magneticum as a living iron chelator induces transferrin receptor 1 upregulation in cancer cells

Interest has grown in harnessing biological agents for cancer treatment as dynamic vectors with enhanced tumor targeting. While bacterial traits such as proliferation in tumors, modulation of an immune response and local secretion of toxins have been well studied, less is known about bacteria as competitors for nutrients. Here, we investigated the use of a bacterial strain as a living iron chelator, competing for this nutrient vital to tumor growth and progression. We established an in vitro co-culture system consisting of the magnetotactic strain Magnetospirillum magneticum AMB-1 incubated under hypoxic conditions with human melanoma cells. Siderophore production by 108 AMB-1/mL in human transferrin (Tf)-supplemented media was quantified and found to be equivalent to a concentration of 3.78 M {+/-} 0.117 M deferoxamine, a potent drug used in iron chelation therapy. Our experiments revealed an increased expression of transferrin receptor 1 (TfR1) and a significant decrease of cancer cell viability, indicating the bacterias ability to alter iron homeostasis in human melanoma cells. Our results show the potential of a bacterial strain acting as a self-replicating iron-chelating agent, which could serve as an additional mechanism reinforcing current bacterial cancer therapies.

cell biology↗

bioRxiv2019

Genetic encoding of targeted MRI contrast agents for in vivo tumor imaging

Tumor-selective contrast agents have the potential to aid in the diagnosis and treatment of cancer using noninvasive imaging modalities such as magnetic resonance imaging (MRI). Such contrast agents can consist of magnetic nanoparticles incorporating functionalities that respond to cues specific to tumor environments. Genetically engineering magnetotactic bacteria to display peptides has been investigated as a means to produce contrast agents that combine the robust image contrast effects of magnetosomes with transgenic targeting peptides displayed on their surface. This work reports the first use of magnetic nanoparticles that display genetically-encoded pH low insertion peptide (pHLIP), a long peptide intended to enhance MRI contrast by targeting the extracellular acidity associated with the tumors. To demonstrate the modularity of this versatile platform to incorporate diverse targeting ligands by genetic engineering, we also incorporated the cyclic v integrin-binding peptide iRGD into separate magnetosomes. Specifically, we investigate their potential for enhanced binding and tumor imaging both in vitro and in vivo. Our experiments indicate that these tailored magnetosomes retain their magnetic properties, making them well-suited as T2 contrast agents, while exhibiting increased binding compared to wild-type magnetosomes.

synthetic biology↗