Effects of Micro-/Nanorobots on Various Microbial Species

Version	Summary	Created by	Modification	Content Size	Created at	Operation
1		Fulden Ulucan Karnak	--	1327	2022-08-17 12:33:29	\|
2	layout	Camila Xu	Meta information modification	1327	2022-08-18 02:36:27	\| \|
3	layout	Camila Xu	-65 word(s)	1262	2022-08-18 02:37:12	\|

This entry is adapted from the peer-reviewed paper 10.3390/prosthesis4030034

One of the most pressing concerns to global public health is the emergence of drug-resistant pathogenic microorganisms due to increased unconscious antibiotic usage. With the rising antibiotic resistance, existing antimicrobial agents lose their effectiveness over time. This indicates that newer and more effective antimicrobial agents and methods should be investigated.

antimicrobial bacterial infections drug resistance microrobots nanorobots autonomous treatment

1. Advantages and Disadvantages of Current Micro-/Nanorobots

People worldwide are struggling with various microbial infections that directly or indirectly cause deadly diseases. The development of antibiotic resistance, especially in bacteria-caused microbial diseases, makes it challenging to fight infectious diseases and results in severe morbidity and mortality in patients. With the help of developments in nanotechnology, micro-/nanorobots appeared as promising treatment tools in the biomedical and pharmaceutical fields. They exhibit tailorable activities according to their shapes, sizes, loads, and surface and physicochemical properties ^[1]. For example, micro-/nanorobots might reach the areas that are difficult to reach in the body, owing to their small size and different shapes. Hence, they can be useful in the future treatments of pathogenic bacteria-based biofilms ^[2]. Researchers have tried to prevent antibiotic resistance by providing specific targeting in antimicrobial studies with nanorobots, so it is thought that higher success can be achieved compared to traditional methods.

Although micro-/nanorobots have several advantages, such as real-time localization that can be provided by using common medical imaging techniques including X-ray, MRI, and ultrasound scans ^[3], there are some points to be critically considered before realizing their usage. The first of these is the delivery path of the given micro-/nanorobots. The navigation distance must be kept as short as possible and biological barriers should be kept in mind while designing, to deliver therapeutics to a targeted region efficiently ^[4]. Ensuring collective control is another issue. Creating collective micro-/nanorobots, which can act cooperatively and closely, while performing different tasks, would significantly improve their missions such as manipulation of objects, which would have high potential in the targeted biofilm disruption ^[5]. Another concern is the actuation or propulsion mechanism, which is divided into external control and chemical. In chemical energy-based motion, motion is achieved by converting chemical energy into mechanical or other forms of chemical energy. Although these micro-/nanorobots provide a high degree of autonomy with chemical energy, there is an increased risk of toxicity unless they are biocompatible ^[6]. Moreover, the fuel-loading capacity of the chemically catalyzed micro-/nanorobots is another factor limiting their long-term applications. The control of micro-/nanorobots by external fields enhances dynamic regulation and decision-making processes, such as motion and swimming speed control to release therapeutics at the right time and in the right place, and in addition, minimizes toxicity ^[7]. Finally, for establishing a long-term safety profile of micro-/nanorobots, the biodegradability, waste profile, immunogenic response, all, biocompatibility of the designed micro-/nanorobots should be carefully tested through animal and clinical trials ^[8]. In this manner, the studies carried out with FDA-approved nanoagents and/or materials make microrobots reliable and promising. Efficient retrieval after the operations is also crucial. For instance, magnetic micro-/nanorobots are recommended to collect back promptly via magnets to minimize damage to healthy tissues. Another important issue in microrobot design is the expenses. While external field-actuated microrobots can move without the need of fuel, for the use in the clinic, the real-life realization of them requires central medical facilities with expensive control systems, and professionally trained healthcare personnel. Thus, it is important to establish cooperation between the fields of medicine and engineering in order to produce microrobots that are biocompatible, therapeutically efficient, sustainable and affordable ^[9].

2. Recent Situation of In Vivo Antimicrobial Studies

In the dynamically developing field of micro-/nanorobots, their anti-microbial applications have also exhibited great enhancements. Consequently, the number of in vivo studies has been growing day by day. For example, in a study by Su et al. P. gingivalis periodontal disease in rats was demonstrated using a MnO₂-based microrobot. In another in vivo study, NIR-driven parachute-like nanomotors loaded with miconazole nitrate (PNM-MN) were injected subcutaneously into mice. Combined with the combination of pharmacological and photothermal effects for the treatment of mice infected with Candida albicans, the mice recovered completely and showed a therapeutic efficacy superior to other treatments ^[10]. In the study conducted with AuNP/mesoporous silica nanorobot containing antibiotics injected into the implantation site of mice infected with S. aerus bacteria, mice were treated within 10 min by magnetic activation without damaging any healthy tissue ^[1]. Similarly, a dextran-coated Fe₃O₄ microrobot was used for the treatment of mice infected with S. mutans ^[11]. Many in vitro studies have been conducted in the water environment or in a liquid that is used as fuel for the catalytic motion, however, their real in vitro efficiency remains unclear.

Considering the above-mentioned in vivo studies, and the advantages and disadvantages of micro-/nanorobots, soon researchers will be witnessing their promising antimicrobial applications in medicine. For example, treatment of resistive infections or biofilms in easier-to-reach body regions for micro-/nanorobots, such as gastrointestinal and urinary tracts, ear, nose, and throat ^[12], could be the starting point, particularly for the autonomous and magnetically actuated systems. In addition, the usage of an external actuation, such as light and/or ultrasound waves, together with the high-technology medical devices would let people develop highly targeted and efficient treatments for subcutaneous, periodontal, and implant-associated infections, owing to their penetration ability through the skin.

3. Application Routes, Limitations, and Future Perspectives

To reach success in the process of antimicrobial treatments, there are crucial elements that must be considered. Mainly, controlling the accumulation of antibacterial drugs at the site of infection, increasing bactericidal therapeutic efficacy, limiting the interactions of antibiotics with the healthy tissue, and reducing toxicity risks, and reducing the killing effect of antibiotics on commensal microflora are pivotal factors to consider when designing carriers for specific and sustainable release of antibiotics. To create better antibiotic delivery systems, an effective strategy would be to create a system that responds to stimuli in one of two ways. In these options, the system either reacts autonomously and recognizes the bacterial environment or is sensitized to certain physical elements. These methods will increase the effectiveness, targeting abilities, and effectiveness of antibiotic treatments while reducing their negative effects ^[13].

One of the main conditions leading to the acceleration of the evolution of MDR and the unselective killing of beneficial bacteria is the tendency of using traditional broad-spectrum antibiotics. A new start-up company, Eligo Bioscience^®, reported that they have been working on creating antimicrobials, whose spectrum and activity can be designed by using CRISPR-Cas (“programmable gene scissors”) technology. The company, which is conducting in vivo studies with carrier devices such as nanorobots, has been focused on delivering RNA-guided nucleases (RGNs) for targeting specific DNA regions in microbial populations. The usage of programmable RGNs might trigger the emergence of alternative antibacterial techniques that impose direct evolutionary pressure at the gene level ^[14]. The design of delivery vehicles such as nanorobots will be important to create RGNs that can target other strains, such as multidrug-resistant pathogens.

In addition to the proven effects of micro-/nanorobots on bacterial species, a few studies mentioned that they could be also used for the treatment of viruses ^[15]. Studies with the SARS-CoV-2 virus, which threatens public health, have shown that micro-/nanorobot applications can be useful for destroying viruses. Micro-/nanorobots can make the transportation of antiviral medicines an effective and simple process due to their modifiable surfaces, speeds, and motion control. The ability to carry antiviral agents, particularly suitable for pandemic and epidemic viruses such as HIV, Herpes, Ebola, ZIKA, and Dengue will open the door to target-specific treatments of these viruses in the future ^[15]^[16].

References

Geelsu Hwang; Amauri J. Paula; Elizabeth E. Hunter; Yuan Liu; Alaa Babeer; Bekir Karabucak; Kathleen Stebe; Vijay Kumar; Edward Steager; Hyun Koo; et al. Catalytic antimicrobial robots for biofilm eradication. Science Robotics 2019, 4, eaaw2388, 10.1126/scirobotics.aaw2388.
Yinglei Zhang; Yuepeng Zhang; Yaqian Han; Xue Gong; Micro/Nanorobots for Medical Diagnosis and Disease Treatment. Micromachines 2022, 13, 648, 10.3390/mi13050648.
Junhee Choi; Junsun Hwang; Jin‐Young Kim; Hongsoo Choi; Recent Progress in Magnetically Actuated Microrobots for Targeted Delivery of Therapeutic Agents. Advanced Healthcare Materials 2020, 10, e2001596, 10.1002/adhm.202001596.
Zhongyi Li; Chunyang Li; Lixin Dong; Jing Zhao; A Review of Microrobot’s System: Towards System Integration for Autonomous Actuation In Vivo. Micromachines 2021, 12, 1249, 10.3390/mi12101249.
Mengyi Hu; Xuemei Ge; Xuan Chen; Wenwei Mao; Xiuping Qian; Wei-En Yuan; Micro/Nanorobot: A Promising Targeted Drug Delivery System. Pharmaceutics 2020, 12, 665, 10.3390/pharmaceutics12070665.
Xiaoguang Dong; Metin Sitti; Controlling two-dimensional collective formation and cooperative behavior of magnetic microrobot swarms. The International Journal of Robotics Research 2020, 39, 617-638, 10.1177/0278364920903107.
Arnab Halder; Yi Sun; Biocompatible propulsion for biomedical micro/nano robotics. Biosensors and Bioelectronics 2019, 139, 111334, 10.1016/j.bios.2019.111334.
Ming Luo; Youzeng Feng; Tingwei Wang; Jianguo Guan; Micro-/Nanorobots at Work in Active Drug Delivery. Advanced Functional Materials 2018, 28, 1706100, 10.1002/adfm.201706100.
Pelin Erkoc; Immihan Ceren Yasa; Hakan Ceylan; Oncay Yasa; Yunus Alapan; Metin Sitti; Mobile Microrobots for Active Therapeutic Delivery. Advanced Therapeutics 2018, 2, 1800064, 10.1002/adtp.201800064.
Xin Ji; Haiyuan Yang; Wen Liu; Yandong Ma; Jinpei Wu; Xiaoqing Zong; Pengfei Yuan; Xinjie Chen; Caiqi Yang; Xiaodi Li; et al.Hongsheng LinWei XueJian Dai Multifunctional Parachute-like Nanomotors for Enhanced Skin Penetration and Synergistic Antifungal Therapy. ACS Nano 2021, 15, 14218-14228, 10.1021/acsnano.1c01379.
Pratap C. Naha; Yuan Liu; Geelsu Hwang; Yue Huang; Sarah Gubara; Venkata Jonnakuti; Aurea Simon-Soro; Dongyeop Kim; Lizeng Gao; Hyun Koo; et al.David P. Cormode Dextran-Coated Iron Oxide Nanoparticles as Biomimetic Catalysts for Localized and pH-Activated Biofilm Disruption. ACS Nano 2019, 13, 4960-4971, 10.1021/acsnano.8b08702.
Ajay Vikram Singh; Mohammad Hasan Dad Ansari; Peter Laux; Andreas Luch; Micro-nanorobots: important considerations when developing novel drug delivery platforms. Expert Opinion on Drug Delivery 2019, 16, 1259-1275, 10.1080/17425247.2019.1676228.
Xinfu Yang; Wenxin Ye; Yajun Qi; Yin Ying; Zhongni Xia; Overcoming Multidrug Resistance in Bacteria Through Antibiotics Delivery in Surface-Engineered Nano-Cargos: Recent Developments for Future Nano-Antibiotics. Frontiers in Bioengineering and Biotechnology 2021, 9, 696514, 10.3389/fbioe.2021.696514.
Robert J Citorik; Mark Mimee; Timothy K Lu; Sequence-specific antimicrobials using efficiently delivered RNA-guided nucleases. Nature Biotechnology 2014, 32, 1141-1145, 10.1038/nbt.3011.
Malobika Chakravarty; Amisha Vora; Nanotechnology-based antiviral therapeutics. Drug Delivery and Translational Research 2020, 11, 748-787, 10.1007/s13346-020-00818-0.
Fangyu Zhang; Zhengxing Li; Lu Yin; Qiangzhe Zhang; Nelly Askarinam; Rodolfo Mundaca-Uribe; Farshad Tehrani; Emil Karshalev; Weiwei Gao; Liangfang Zhang; et al.Joseph Wang ACE2 Receptor-Modified Algae-Based Microrobot for Removal of SARS-CoV-2 in Wastewater. Journal of the American Chemical Society 2021, 143, 12194-12201, 10.1021/jacs.1c04933.

© Text is available under the terms and conditions of the Creative Commons Attribution (CC BY) license; additional terms may apply. By using this site, you agree to the Terms and Conditions and Privacy Policy.

Upload a video for this entry

Information

Subjects: Nanoscience & Nanotechnology

Contributors MDPI registered users' name will be linked to their SciProfiles pages. To register with us, please refer to https://encyclopedia.pub/register :

Mustafa Sami Ozaydin

Lorin Doganturk

Fulden Ulucan-Karnak

Ozan Akdogan

Pelin Erkoc

View Times: 391

Update Date: 23 Aug 2022

Table of Contents

Video Upload Options

Confirm

1. Advantages and Disadvantages of Current Micro-/Nanorobots

2. Recent Situation of In Vivo Antimicrobial Studies

3. Application Routes, Limitations, and Future Perspectives

References