Magnetically steerable bacterial microrobots moving in 3D biological matrices for stimuli-responsive cargo delivery

Akolpoglu, Mukrime Birgul; Alapan, Yunus; Dogan, Nihal Olcay; Baltaci, Saadet Fatma; Yaşa, Öncay; Tural, Gulsen Aybar; Sitti, Metin

doi:10.1126/sciadv.abo6163

Cited by 121 publications

(114 citation statements)

References 60 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Of these, magnetic fields are especially promising for medical use because of their minimally invasive deep tissue penetration and well-established clinical safety ( 17 ). Magnetically responsive bacteria include strains rendered magnetic through conjugation with magnetic materials ( 18 – 20 ) and magnetotactic bacteria (MTB), which are innately magnetic. In their native aquatic habitats, MTB typically biomineralize stably magnetized anisotropic chains of magnetite nanocrystals and use magnetically assisted aerotaxis to migrate to regions of low oxygen concentration.…”

Section: Introductionmentioning

confidence: 99%

Magnetic torque–driven living microrobots for increased tumor infiltration

et al. 2022

View full text Add to dashboard Cite

Biohybrid bacteria–based microrobots are increasingly recognized as promising externally controllable vehicles for targeted cancer therapy. Magnetic fields in particular have been used as a safe means to transfer energy and direct their motion. Thus far, the magnetic control strategies used in this context rely on poorly scalable magnetic field gradients, require active position feedback, or are ill-suited to diffuse distributions within the body. Here, we present a magnetic torque–driven control scheme for enhanced transport through biological barriers that complements the innate taxis toward tumor cores exhibited by a range of bacteria, shown for Magnetospirillum magneticum as a magnetically responsive model organism. This hybrid control strategy is readily scalable, independent of position feedback, and applicable to bacterial microrobots dispersed by the circulatory system. We observed a fourfold increase in translocation of magnetically responsive bacteria across a model of the vascular endothelium and found that the primary mechanism driving increased transport is torque-driven surface exploration at the cell interface. Using spheroids as a three-dimensional 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 that our control scheme offers further advantages, including the possibility for closed-loop optimization based on inductive detection, as well as spatially selective actuation to reduce off-target effects. Last, after systemic intravenous injection in mice, we showed significantly increased bacterial tumor accumulation, supporting the feasibility of deploying this control scheme clinically for magnetically responsive biohybrid microrobots.

show abstract

Section: Introductionmentioning

confidence: 99%

Magnetic torque–driven living microrobots for increased tumor infiltration

et al. 2022

View full text Add to dashboard Cite

show abstract

“…Although bacteria have been extensively used as actuators in the design of biohybrid MNRs, their possible acute toxicity and rapid growth in physiological environments limit their clinical application. Therefore, novel biohybrid MNRs with higher biocompatibility are highly desired for application in tumor-targeted therapy (Akolpoglu et al, 2022). Alapan and coworkers developed a multifunctional biohybrid micromotor composed of bioengineered bacteria (E. coli MG1655) and RBCs loaded with model drugs (i.e., DOX) and superparamagnetic iron oxide nanoparticles (Alapan et al, 2018) (Figure 9D).…”

Section: Bacteria-based Micro/nanorobotsmentioning

confidence: 99%

“Motile-targeting” drug delivery platforms based on micro/nanorobots for tumor therapy

Zhang

Liu

Guan

et al. 2022

Front. Bioeng. Biotechnol.

View full text Add to dashboard Cite

Traditional drug delivery systems opened the gate for tumor-targeted therapy, but they generally took advantage of enhanced permeability and retention or ligand-receptor mediated interaction, and thus suffered from limited recognition range (<0.5 nm) and low targeting efficiency (0.7%, median). Alternatively, micro/nanorobots (MNRs) may act as emerging “motile-targeting” drug delivery platforms to deliver therapeutic payloads, thereby making a giant step toward effective and safe cancer treatment due to their autonomous movement and navigation in biological media. This review focuses on the most recent developments of MNRs in “motile-targeting” drug delivery. After a brief introduction to traditional tumor-targeted drug delivery strategies and various MNRs, the representative applications of MNRs in “motile-targeting” drug delivery are systematically streamlined in terms of the propelling mechanisms. Following a discussion of the current challenges of each type of MNR in biomedical applications, as well as future prospects, several promising designs for MNRs that could benefit in “motile-targeting” drug delivery are proposed. This work is expected to attract and motivate researchers from different communities to advance the creation and practical application of the “motile-targeting” drug delivery platforms.

show abstract

“…Controllable and precise cell transportation is of significant interest concerning desirable therapy, for example, targeted cell study and transport, for which two methods, contact and non-contact, can be realized. [46,47] In order to accomplish a flexible operation in the defined surroundings, the non-contact manipulation of microrobots holds great advantages in non-contamination and remote control for biological applications. By regulating the parameters of the external rotating magnetic field, the locomotion of hematite microrobots possesses the feature of flexible and remote control.…”

Section: Forschungsartikelmentioning

confidence: 99%

Self‐Propelled Magnetic Dendrite‐Shaped Microrobots for Photodynamic Prostate Cancer Therapy

et al. 2022

View full text Add to dashboard Cite

Photocatalytic micromotors that exhibit wireless and controllable motion by light have been extensively explored for cancer treatment by photodynamic therapy (PDT). However, overexpressed glutathione (GSH) in the tumor microenvironment can down‐regulate the reactive oxygen species (ROS) level for cancer therapy. Herein, we present dendrite‐shaped light‐powered hematite microrobots as an effective GSH depletion agent for PDT of prostate cancer cells. These hematite microrobots can display negative phototactic motion under light irradiation and flexible actuation in a defined path controlled by an external magnetic field. Non‐contact transportation of micro‐sized cells can be achieved by manipulating the microrobot's motion. In addition, the biocompatible microrobots induce GSH depletion and greatly enhance PDT performance. The proposed dendrite‐shaped hematite microrobots contribute to developing dual light/magnetic field‐powered micromachines for the biomedical field.

show abstract

Magnetically steerable bacterial microrobots moving in 3D biological matrices for stimuli-responsive cargo delivery

Cited by 121 publications

References 60 publications

Magnetic torque–driven living microrobots for increased tumor infiltration

Magnetic torque–driven living microrobots for increased tumor infiltration

“Motile-targeting” drug delivery platforms based on micro/nanorobots for tumor therapy

Self‐Propelled Magnetic Dendrite‐Shaped Microrobots for Photodynamic Prostate Cancer Therapy

Contact Info

Product

Resources

About