DEVELOPMENT AND APPLICATIONS OF MICRO-AND NANOROBOTICS IN DRUG DELIVERY
DOI:
https://doi.org/10.22159/ijap.2023v15i5.38074Keywords:
Micro or nanorobots, Targeted delivery, Actuation, Design, DevelopmentAbstract
Micro-and nanorobotics is a new field of research that emerged from the fusion of micro/nanotechnology and robotics and has since acquired enormous importance. The advantages of micro-and nanorobots include their small dimension, lightweight, high flexibility, and high sensitivity. Micro-and nanorobots have sparked the scientific community's interest in research and opened up a broad variety of application areas, including medication delivery and disease diagnostics, due to their differences from macroscopic robots. Over the past 30 y, research on micro-and nanorobots has made major strides. This manuscript provides a detailed explanation of the development of these robots. Then, each of the primary robot components including their actuation, design, production, and control is discussed separately. Additionally, potential challenges in developing such robots are explored from the perspectives of intelligence and sensing, therapeutic applications, materials, and performance.
Downloads
References
Panwar N. Nanobots: a nanomachine with potential applications. J Pharm Nanotechnol Res Rev. 2015;3(1):43-6.
Singh AV, Ansari MHD, Laux P, Luch A. Micro-nanorobots: important considerations when developing novel drug delivery platforms. Expert Opin Drug Deliv. 2019;16(11):1259-75. doi: 10.1080/17425247.2019.1676228, PMID 31580731.
Playter R, Buehler M, Bigdog RM. In: The proceedings of the unmanned systems technology VIII: International society for the optics and photonics. Orlando: SPIE-International Society for Optical Engineering; 2006. p. 62302O.
Soto F, Chrostowski R. Frontiers of medical micro/nanorobotics: in vivo applications and commercialization perspectives toward clinical uses. Front Bioeng Biotechnol. 2018;6:170. doi: 10.3389/fbioe.2018.00170. PMID 30488033.
Pharasi D. Nanomedicine: a brief note. Nanotechnol Lett. 2022;7(5):20-1. doi: 10.37532.pulnl.22.7(5).20-21.
Wu Z, Troll J, Jeong HH, Wei Q, Stang M, Ziemssen F. A swarm of slippery micropropellers penetrates the vitreous body of the eye. Sci Adv. 2018;4(11):eaat4388. doi: 10.1126/sciadv.aat4388.
Qiu F, Nelson BJ. Magnetic helical micro-and nanorobots: toward their biomedical applications. Engineering. 2015;1(1):21-6. doi: 10.15302/J-ENG-2015005.
Zhang MJ, Tarn TJ, Micro XN. In: IEEE International Conference on Robotics and Automation. 2004;2:2068-73. doi: 10.1109/ROBOT.2004.1308128.
Medina Sanchez M, Xu HF, Schmidt OG. Micro-and nano-motors: the new generation of drug carriers. Ther Deliv. 2018;9(4):303-16. doi: 10.4155/tde-2017-0113, PMID 29540126.
Chen XZ, Hoop M, Shamsudhin N, Huang T, Ozkale B, Li Q. Hybrid magnetoelectric nanowires for nanorobotic applications: fabrication, magnetoelectric coupling, and magnetically assisted in vitro targeted drug delivery. Adv Mater. 2017;29(8):1605458. doi: 10.1002/adma.201605458, PMID 27943524.
Douglas SM, Bachelet I, Church GM. A logic-gated nanorobot for targeted transport of molecular payloads. Science. 2012;335(6070):831-4. doi: 10.1126/science.1214081, PMID 22344439.
Ullrich F, Bergeles C, Pokki J, Ergeneman O, Erni S, Chatzipirpiridis G. Mobility experiments with microrobots for minimally invasive intraocular surgery. Invest Ophthalmol Vis Sci. 2013;54(4):2853-63. doi: 10.1167/iovs.13-11825, PMID 23518764.
Davis ME, Chen ZG, Shin DM. Nanoparticle therapeutics: an emerging treatment modality for cancer. Nat Rev Drug Discov. 2008;7(9):771-82. doi: 10.1038/nrd2614, PMID 18758474.
Verma SK, Chauhan R. Nanorobotics in dentistry–a review. Ind J Dent. 2014;5(7):62-70. doi: 10.1016/j.ijd.2012.12.010.
Cavalcanti A, Shirinzadeh B, Kretly LC. Medical nanorobotics for diabetes control. Nanomedicine. 2008;4(2):127-38. doi: 10.1016/j.nano.2008.03.001. PMID 18455965.
Cavalcanti A, Rosen L, Shirinzadeh B. Nanorobot for treatment of patients with artery occlusion. In: Proceedings of the Virtual concept. Cancun. Springer; 2006. p. 1-10.
Schalley CA, Beizai K, Vogtle F. On the way to rotaxane-based molecular motors: studies in molecular mobility and topological chirality. Acc Chem Res. 2001;34(6):465-76. doi: 10.1021/ar000179i, PMID 11412083.
Bhushan B. Biomimetics: lessons from nature–an overview. Philos Trans A Math Phys Eng Sci. 2009;367(1893):1445-86. doi: 10.1098/rsta.2009.0011, PMID 19324719.
Cho KJ, Koh JS, Kim S, Chu W, Hong Y, Ahn S. Review of manufacturing processes for soft biomimetic robots. Int J Precis Eng Manuf. 2009;10(3):171-81. doi: 10.1007/s12541-009-0064-6.
Chu WS, Lee KT, Song SH, Han M, Lee J, Kim H. Review of biomimetic underwater robots using smart actuators. Int J Precis Eng Manuf. 2012;13(7):1281-92. doi: 10.1007/s12541-012-0171-7.
Ghosh A, Fischer P. Controlled propulsion of artificial magnetic nanostructured propellers. Nano Lett. 2009;9(6):2243-5. doi: 10.1021/nl900186w, PMID 19413293.
Dreyfus R, Baudry J, Roper ML, Fermigier M, Stone HA, Bibette J. Microscopic artificial swimmers. Nature. 2005;437(7060):862-5. doi: 10.1038/nature04090, PMID 16208366.
Ricotti L, Trimmer B, Feinberg AW, Raman R, Parker KK, Bashir R. Biohybrid actuators for robotics: a review of devices actuated by living cells. Sci Robot. 2017;2(12):eaaq0495. doi: 10.1126/scirobotics.aaq0495. PMID 33157905.
Medina Sanchez M, Schwarz L, Meyer AK, Hebenstreit F, Schmidt OG. Cellular cargo delivery: toward assisted fertilization by sperm-carrying micromotors. Nano Lett. 2016;16(1):555-61. doi: 10.1021/acs.nanolett.5b04221. PMID 26699202.
Diller E. Micro scale mobile robotics. FNT in Robotics. 2011;2(3):143-259. doi: 10.1561/2300000023.
Stanton MM, Trichet Paredes C, Sanchez S. Applications of three-dimensional (3D) printing for microswimmers and bio-hybrid robotics. Lab Chip. 2015;15(7):1634-7. doi: 10.1039/C5LC90019K, PMID 25632887.
Horiguchi H, Imagawa K, Hoshino T, Akiyama Y, Morishima K. Fabrication and evaluation of reconstructed cardiac tissue and its application to bio-actuated microdevices. IEEE Trans Nanobioscience. 2009;8(4):349-55. doi: 10.1109/TNB.2009.2035282, PMID 20142148.
Pokki J, Ergeneman O, Sivaraman KM, Ozkale B, Zeeshan MA, Luhmann T. Electroplated porous polypyrrole nanostructures patterned by colloidal lithography for drug-delivery applications. Nanoscale. 2012;4(10):3083-8. doi: 10.1039/C2NR30192J, PMID 22422198.
Hu C, Aeschlimann F, Chatzipirpiridis G, Pokki J, Chen X, Puigmarti Luis J. Spatiotemporally controlled electrodeposition of magnetically driven micromachines based on the inverse opal architecture. Electrochem Commun. 2017;81:97-101. doi: 10.1016/j.elecom.2017.06.012.
Choi JW, MacDonald E, Wicker R. Multi-material micro stereolithography. Int J Adv Manuf Technol. 2010;49(5-8):543-51. doi: 10.1007/s00170-009-2434-8.
Lan PX, Lee JW, Seol YJ, Cho DW. Development of 3D PPF/DEF scaffolds using micro-stereolithography and surface modification. J Mater Sci Mater Med. 2009;20(1):271-9. doi: 10.1007/s10856-008-3567-2, PMID 18763023.
Gao W, Feng X, Pei A, Kane CR, Tam R, Hennessy C. Bioinspired helical microswimmers based on vascular plants. Nano Lett. 2014;14(1):305-10. doi: 10.1021/nl404044d, PMID 24283342.
Wang Y, Fei ST, Byun YM, Lammert PE, Crespi VH, Sen A. Dynamic interactions between fast microscale rotors. J Am Chem Soc. 2009;131(29):9926-7. doi: 10.1021/ja904827j, PMID 19572715.
He Y, Wu J, Zhao Y. Designing catalytic nanomotors by dynamic shadowing growth. Nano Lett. 2007;7(5):1369-75. doi: 10.1021/nl070461j, PMID 17430007.
Darnton N, Turner L, Breuer K, Berg HC. Moving fluid with bacterial carpets. Biophys J. 2004;86(3):1863-70. doi: 10.1016/S0006-3495(04)74253-8, PMID 14990512.
Lin X, Wu Z, Wu Y, Xuan M, He Q. Self-propelled micro-/nanomotors based on controlled assembled architectures. Adv Mater. 2016;28(6):1060-72. doi: 10.1002/adma.201502583, PMID 26421653.
Khalil ISM, Dijkslag HC, Abelmann L, Misra S. Magnetosperm: a microrobot that navigates using weak magnetic fields. Appl Phys Lett. 2014;104(22):223701-223701-4. doi: 10.1063/1.4880035.
Rajagopalan J, Saif MTA. Fabrication of freestanding 1-D PDMS microstructures using capillary micromolding. J Microelectromech Syst. 2013;22(5):992-4. doi: 10.1109/JMEMS.2013.2262605.
Chen K, Gu C, Yang Z, Nakajima M, Chen T, Fukuda T. “Z”-Shaped rotational Au/Pt micro-nanorobot. Micromachines. 2017;8(6):183. doi: 10.3390/mi8060183.
Zhou D, Li YC, Xu P, Ren L, Zhang G, Mallouk TE. Visible-light driven Si-Au micromotors in water and organic solvents. Nanoscale. 2017;9(32):11434-8. doi: 10.1039/c7nr04161f, PMID 28786464.
Hong Y, Velegol D, Chaturvedi N, Sen A. Biomimetic behavior of synthetic particles: from microscopic randomness to macroscopic control. Phys Chem Chem Phys. 2010;12(7):1423-35. doi: 10.1039/Bb9197741Hh, PMID 20126754.
Ahmed S, Wang W, Mair LO, Fraleigh RD, Li S, Castro LA. Steering acoustically propelled nanowire motors toward cells in a biologically compatible environment using magnetic fields. Langmuir. 2013;29(52):16113-8. doi. org/10.1021/la403946j, PMID 24345038.
Li T, Chang X, Wu Z, Li J, Shao G, Deng X. Autonomous collision-free navigation of microvehicles in complex and dynamically changing environments. ACS Nano. 2017;11(9):9268-75. doi: 10.1021/acsnano.7b04525, PMID 28803481.
Tottori S, Zhang L, Qiu F, Krawczyk KK, Franco Obregon A, Nelson BJ. Magnetic helical micromachines: fabrication, controlled swimming, and cargo transport. Adv Mater. 2012;24(6):811-6. doi: 10.1002/adma.201103818, PMID 22213276.
Laocharoensuk R, Burdick J, Wang J. Carbon-nanotube-induced acceleration of catalytic nanomotors. ACS Nano. 2008;2(5):1069-75. doi: 10.1021/nn800154g, PMID 19206505.
Kim K, Liu X, Zhang Y, Sun Y. Nanonewton force-controlled manipulation of biological cells using a monolithic MEMS microgripper with two-axis force feedback. J Micromech Microeng. 2008;18(5):055013. doi: 10.1088/0960-1317/18/5/055013.
Yang GZ, Bellingham J, Dupont PE, Fischer P, Floridi L, Full R. The grand challenges of science robotics. Sci Robot. 2018;3(14):eaar7650. doi: 10.1126/scirobotics.aar7650. aar7650, PMID 33141701.
Teo WZ, Wang H, Pumera M. Beyond platinum: silver-catalyst based bubble-propelled tubular micromotors. Chem Commun (Camb). 2016;52(23):4333-6. doi: 10.1039/C6CC00115G, PMID 26923278.
Zhang C, Wang W, Xi N, Wang Y, Liu L. Development and future challenges of bio-syncretic robots. Engineering. 2018;4(4):452-63. doi: 10.1016/j.eng.2018.07.005.
Steager EB, Selman Sakar M, Magee C, Kennedy M, Cowley A, Kumar V. Automated biomanipulation of single cells using magnetic microrobots. Int J Robot Res. 2013;32(3):346-59. doi: 10.1177/0278364912472381.
Li T, LiJ, Zhang H, Chang X, Song W, Hu Y, Shao G, Sandraz E, Zhang G, Li L, Wang J. Magnetically propelled fish-like nano swimmers. Small. 2016;12:32-8. doi: 10.1002/smll.201601846.
Fan D, Yin Z, Cheong R, Zhu FQ, Cammarata RC, Chien CL. Subcellular-resolution delivery of a cytokine through precisely manipulated nanowires. Nat Nanotechnol. 2010;5(7):545-51. doi: 10.1038/nnano.2010.104, PMID 20543835.
Demirors AF, AF Akan MT, Poloni E, Studart AR. Active cargo transport with Janus colloidal shuttles using electric and magnetic fields. Soft Matter. 2018;14(23):4741-9. doi: 10.1039/C8SM00513C, PMID 29799053.
Jeong J, Jang D, Kim D, Lee D, Chung SK. Sensors and actuators b: chemical. Sens Actuators. 2020;306:11197355.
Liang Z, Teal D, Fan DE. Light-programmable micro/nanomotors with optically tunable in-phase electric polarization. Nat Commun. 2019;10(1):5275. doi: 10.1038/s41467-019-13255-6, PMID 31754176.
Si W, Yu M, Wu G, Chen C, Sha J, Zhang Y, Chen Y. A nanoparticle-DNA assembled nanorobot powered by charge-tunable quad-nanopore system. ACS Nano. 2020;14(11):15349-60. doi: 10.1021/acsnano.0c05779, PMID 33151055.
Wang W, Wu Z, Lin X, Si T, He Q. Gold-nanoshell-functionalized polymer nano swimmer for photomechanical poration of single-cell membrane. J Am Chem Soc. 2019;141(16):6601-8. doi: 10.1021/jacs.8b13882. PMID 30943720.
Magdanz V, Sanchez S, Schmidt OG. Development of a sperm-flagella-driven micro-bio-robot. Adv Mater. 2013;25(45):6581-8. doi: 10.1002/adma.201302544. PMID 23996782.
Bogunia Kubik K, Sugisaka M. From molecular biology to nanotechnology and nanomedicine. Biosystems. 2002;65(2-3):123-38. doi: 10.1016/s0303-2647(02)00010-2. PMID 12069723.
Freitas RA Jr. Exploratory design in medical nanotechnology: a mechanical artificial red cell. Artificial cells, blood substitutes, and immobilization. Biotechnology. 1998;26(4):411-30. doi: 10.3109/10731199809117682, PMID 9663339.
Hurria A, Naylor M, Cohen HJ. Improving the quality of cancer care in an aging population: recommendations from an IOM report. JAMA. 2013;310(617):1795-6. doi: 10.1001/jama.2013.280416, PMID 24193075.
Schreiber GB, Busch MP, Kleinman SH, Korelitz JJ. The risk of transfusion-transmitted viral infections. The Retrovirus Epidemiology Donor Study. N Engl J Med. 1996;334(26):1685-90. doi: 10.1056/NEJM199606273342601, PMID 8637512.
Freitas RA Jr. What is nanomedicine? Nanomedicine Nanomedicine: Nanotechnology Biology and Medicine. 2005;1(1):2-9. doi: 10.1016/j.nano.2004.11.003.
Chang WC, Hawkes EA, Kliot M, Sretavan DW. In vivo use of a nano knife for axon microsurgery. Neurosurgery. 2007;61(4):683-91. doi: 10.1227/01.NEU.0000298896.31355.80, PMID 17986929.
Sretavan DW, Chang W, Hawkes E, Keller C, Kliot M. Microscale surgery on single axons. Neurosurgery. 2005;57(4):635-46. doi: 10.1227/01.NEU.0000175545.57795.ac, PMID: 16239875.
Broderick JP, Brott TG, Duldner JE, Tomsick T, Leach A. Initial and recurrent bleeding are the major causes of death following subarachnoid hemorrhage. Stroke. 1994; 25(7):1342-7. doi: 10.1161/01.str.25.7.1342, PMID 8023347.
Cavalcanti A, Shirinzadeh B, Fukuda T, Ikeda S. Nanorobot for brain aneurysm. The International Journal of Robotics Research. 2009;28(4):558-70. doi: 10.116177/01278364908097586.str.25.7.1342.
Reuveni T, Motiei M, Romman Z, Popovtzer A, Popovtzer R. Targeted gold nanoparticles enable molecular CT imaging of cancer: an in vivo study. Int J Nanomedicine. 2011;6:2859-64. doi: 10.2147/IJN.S25446. S25446. PMID 22131831.
Hogg T, Freitas RA Jr. Chemical power for microscopic robots in capillaries. Nanomedicine. 2010;6(2):298-317. doi: 10.1016/j.nano.2009.10.002, PMID 19836466.
Jeschke S, Nambirajan T, Leeb K, Ziegerhofer J, Sega W, Janetschek G. Detection of early lymph node metastases in prostate cancer by laparoscopic radioisotope guided sentinel lymph node dissection. J Urol. 2005;173(6):1943-6. doi: 10.1097/01.ju.0000158159.16314.eb, PMID 15879787.
Cavalcanti A, Shirinzadeh B, Murphy D, Smith JA. Nanorobots for laparoscopic cancer surgery, nanorobots for laparoscopic cancer surgery, Institute of Electrical and Electronics Engineers. Inst Elec Elect Eng. 2007;7(2):738-43.
Sahoo SK, Parveen S, Panda JJ. The present and future of nanotechnology in human health care. Nanomedicine. 2007;3(1):20-31. doi: 10.1016/j.nano.2006.11.008, PMID 17379166.
Patil M, Mehta DS, Guvva S. Future impact of nanotechnology on medicine and dentistry. J Indian Soc Periodontol. 2008;12(2):34-40. doi: 10.4103/0972-124X.44088, PMID 20142942.
Sule T, Pelin O, Ozak ST, Ozkan P. Nanotechnology and dentistry. Eur J Dent. 2013;7(1):145-51. PMID 23408486.
Absi EG, Addy M, Adams D. Dentine hypersensitivity. A study of the patency of dentinal tubules in sensitive and non-sensitive cervical dentine. J Clin Periodontol. 1987;14(25):280-4. doi: 10.1111/j.1600-051x.1987.tb01533.x, PMID 3475295.
Moezizadeh M. Future of dentistry, nano dentistry, ozone therapy and tissue engineering. Journal of Developmental Biology and Tissue Engineering. 2013;5(1):1-6.
Richling B. History of endovascular surgery: personal accounts of the evolution. Neurosurgery. 2006;59(15)Suppl 3:S30-8. doi: 10.5897/JDBTE11227/01.NEU.00100226224.79768.83, PMID 17053616.
Hede S, Huilgol N. "Nano”: The new nemesis of cancer. J Cancer Res Ther. 2006;2(4):186-95. doi: 10.4103/0973-1482.29829, PMID 17998702.
Sivasankar M. Brief review on nanorobots in biomedical applications. Adv Robot Autom. 2012;1(1):1-4. doi: 10.4172/2168-9695.1000101.
Leonardo R, Andrea, Veronica I, Lorenzo V, Ariana M, Ricotti L, Cafarelli A, Iacovacci V, Vannozzi L, Menciassi A. Advanced micro-nano-bio systems for future targeted therapies. Cnano. 2015;11(2):144-60. doi: 10.2174/1573413710666141114221246.
Yu Lv Y, Ruochen Pu R, Yining Tao Y, Xiyu Yang X, Haoran Mu H, Hongsheng Wang H, Wei Sun. Applications and future prospects of micro/nanorobots utilizing diverse biological carriers. Micromachines (Basel). 2023;14(5):983. doi: 10.3390/mi14050983, PMID 37241607.
Sebu NM, Regimol V. Effect of nebulized dexmedetomidine on hemodynamic response to intubation. Asian J Pharm Clin Res. 2023;16(3):155-8. doi: 10.22159/ajpcr.2023.v16i3.47739.
George PP. A mini-review on preparation, characterization, and applications of silver iodide nanoparticles. Asian J Pharm Clin Res. 2022;15(2):11-7. doi: 10.22159/ajpcr.2022.v15i2.43101.
Published
How to Cite
Issue
Section
Copyright (c) 2023 ARCHANA DHYANI, JYOTSNA BHATT, NARDEV SINGH, ASHISH DHYANI
This work is licensed under a Creative Commons Attribution 4.0 International License.
