Multifunctional and biodegradable self-propelled protein motors

Pena‐Francesch, Abdon; Giltinan, Joshua; Sitti, Metin

doi:10.1038/s41467-019-11141-9

Cited by 98 publications

(101 citation statements)

References 50 publications

(59 reference statements)

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“…[ 1 – 3 ] They have potential to offer transformative solutions for non-invasive, local and active medical diagnosis, therapy and intervention, as their small sizes allow them to navigate inside the deep and hard-to-reach regions of the human body. [ 4 , 5 ] A myriad of microscale mobile robots has been developed in recent years, with different actuation strategies, including magnetic,[ 6 , 7 ] electric,[ 8 ] acoustic,[ 9 , 10 ] photo-,[ 11 , 12 ] thermal,[ 13 , 14 ] and chemical[ 14 – 17 ] actuation, for diverse medical applications,[ 1 , 2 ] such as targeted drug delivery, minimally invasive surgery, and remote sensing. However, many scientific challenges lie ahead before such untethered microrobots are ready for clinical use, such as biocompatibility, biodegradation, navigation in complex biofluids, or penetration of biological barriers.…”

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confidence: 99%

Zwitterionic 3D‐Printed Non‐Immunogenic Stealth Microrobots

et al. 2020

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acoustic, [9,10] photo-, [11,12] thermal, [13,14] and chemical [14-17] actuation, for diverse medical applications, [1,2] such as targeted drug delivery, minimally invasive surgery, and remote sensing. However, many scientific challenges lie ahead before such untethered microrobots are ready for clinical use, such as biocompatibility, biodegradation, navigation in complex biofluids, or penetration of biological barriers. [18] Among them, robot interaction with the immune system is a major concern that hurdles their medical operation for long durations. The immune system is prepared to neutralize foreign organisms or materials as a natural protective mechanism, and microrobots are not an exception. When a microrobot enters the body (e.g., bloodstream), it would be rapidly coated with proteins via non-specific adsorption. [19-22] Macrophages, a type of immune cells that are on the lookout for pathogens, recognize these protein-coated materials as foreign threats and become activated, [19] leading to microrobot phagocytosis [23-25] (clearing them and disabling their functions) and eliciting an immune response. Therefore, the activation of macrophages is a major obstacle for developing functional medical microrobots that can operate in vivo for prolonged time. In order to surpass this first innate defense mechanism, we aim to prevent non-specific protein adsorption on the microrobot surface and avoid their detection by macrophages, Microrobots offer transformative solutions for non-invasive medical interventions due to their small size and untethered operation inside the human body. However, they must face the immune system as a natural protection mechanism against foreign threats. Here, non-immunogenic stealth zwitterionic microrobots that avoid recognition from immune cells are introduced. Fully zwitterionic photoresists are developed for two-photon polymerization 3D microprinting of hydrogel microrobots with ample functionalization: tunable mechanical properties, anti-biofouling and non-immunogenic properties, functionalization for magnetic actuation, encapsulation of biomolecules, and surface functionalization for drug delivery. Stealth microrobots avoid detection by macrophage cells of the innate immune system after exhaustive inspection (>90 hours), which has not been achieved in any microrobotic platform to date. These versatile zwitterionic materials eliminate a major roadblock in the development of biocompatible microrobots, and will serve as a toolbox of non-immunogenic materials for medical microrobot and other device technologies for bioengineering and biomedical applications.

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confidence: 99%

Zwitterionic 3D‐Printed Non‐Immunogenic Stealth Microrobots

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“…Internal removal of microrobots produced from biodegradable materials represents another strategy, allowing the microrobots to be cleared for example by surrounding enzymes (e.g., hyaluronidases, acrosins, collagenase, trypsin, etc. ), and/or local pH-or temperature-dependent processes 64,186,187 , as illustrated recently for instance for stomatocytes 64 . However, remaining subproducts and coating materials could still induce undesired immunoreactions or toxicity effects.…”

Section: Translatability Challengesmentioning

confidence: 80%

Engineering microrobots for targeted cancer therapies from a medical perspective

et al. 2020

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Systemic chemotherapy remains the backbone of many cancer treatments. Due to its untargeted nature and the severe side effects it can cause, numerous nanomedicine approaches have been developed to overcome these issues. However, targeted delivery of therapeutics remains challenging. Engineering microrobots is increasingly receiving attention in this regard. Their functionalities, particularly their motility, allow microrobots to penetrate tissues and reach cancers more efficiently. Here, we highlight how different microrobots, ranging from tailor-made motile bacteria and tiny bubble-propelled microengines to hybrid spermbots, can be engineered to integrate sophisticated features optimised for precision-targeting of a wide range of cancers. Towards this, we highlight the importance of integrating clinicians, the public and cancer patients early on in the development of these novel technologies.

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“…Currently, several studies have demonstrated that targeted drug delivery using magnetic driving and biodegradation of microrobots are possible through in vitro and in vivo experiments. [ 15–21,63 ] However, because the microrobots are in direct contact with tissue, local toxicity can be induced. [ 15,22 ] In addition, the degraded products of the microrobot can cause an inflammatory reaction through a pH change in the body.…”

Section: Discussionmentioning

confidence: 99%

A Magnetically Guided Self‐Rolled Microrobot for Targeted Drug Delivery, Real‐Time X‐Ray Imaging, and Microrobot Retrieval

Nguyen

Jin

et al. 2021

Adv Healthcare Materials

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Targeted drug delivery using a microrobot is a promising technique capable of overcoming the limitations of conventional chemotherapy that relies on body circulation. However, most studies of microrobots used for drug delivery have only demonstrated simple mobility rather than precise targeting methods and prove the possibility of biodegradation of implanted microrobots after drug delivery. In this study, magnetically guided self‐rolled microrobot that enables autonomous navigation‐based targeted drug delivery, real‐time X‐ray imaging, and microrobot retrieval is proposed. The microrobot, composed of a self‐rolled body that is printed using focused light and a surface with magnetic nanoparticles attached, demonstrates the loading of doxorubicin and an X‐ray contrast agent for cancer therapy and X‐ray imaging. The microrobot is precisely mobilized to the lesion site through automated targeting using magnetic field control of an electromagnetic actuation system under real‐time X‐ray imaging. The photothermal effect using near‐infrared light reveals rapid drug release of the microrobot located at the lesion site. After drug delivery, the microrobot is recovered without potential toxicity by implantation or degradation using a magnetic‐field‐switchable coiled catheter. This microrobotic approach using automated control method of the therapeutic agents‐loaded microrobot has potential use in precise localized drug delivery systems.

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Multifunctional and biodegradable self-propelled protein motors

Cited by 98 publications

References 50 publications

Zwitterionic 3D‐Printed Non‐Immunogenic Stealth Microrobots

Zwitterionic 3D‐Printed Non‐Immunogenic Stealth Microrobots

Engineering microrobots for targeted cancer therapies from a medical perspective

A Magnetically Guided Self‐Rolled Microrobot for Targeted Drug Delivery, Real‐Time X‐Ray Imaging, and Microrobot Retrieval

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