Intelligent, self-powered, drug delivery systems.

Self-propelled nano/micromotors and pumps are considered to be next generation drug delivery systems since the carriers can either propel themselves ("motor"-based drug delivery) or be delivered ("pump"-based drug delivery) to the target in response to specific biomarkers. Recently, there has been significant advancement towards developing nano/microtransporters into proof-of-concept tools for biomedical applications. This review encompasses the progress made to date on the design of synthetic nano/micromotors and pumps with respect to transportation and delivery of cargo at specific locations. Looking ahead, it is possible to imagine a day when intelligent machines navigate through the human body and perform challenging tasks.

[1]  Kinam Park,et al.  Environment-sensitive hydrogels for drug delivery , 2001 .

[2]  J. L. Anderson,et al.  Transport Mechanisms of Biological Colloids a , 1986, Annals of the New York Academy of Sciences.

[3]  Thomas E Mallouk,et al.  Schooling behavior of light-powered autonomous micromotors in water. , 2009, Angewandte Chemie.

[4]  Joseph Wang,et al.  Can man-made nanomachines compete with nature biomotors? , 2009, ACS nano.

[5]  Jonathan D Posner,et al.  Synthetic nanomotors in microchannel networks: directional microchip motion and controlled manipulation of cargo. , 2008, Journal of the American Chemical Society.

[6]  Henry Hess,et al.  A Biomimetic, Self‐Pumping Membrane , 2010, Advanced materials.

[7]  Ming Zhou,et al.  Dynamic isolation and unloading of target proteins by aptamer-modified microtransporters. , 2011, Analytical chemistry.

[8]  Ayusman Sen,et al.  Fantastic voyage: designing self-powered nanorobots. , 2012, Angewandte Chemie.

[9]  G. Stemme,et al.  A valveless diffuser/nozzle-based fluid pump , 1993 .

[10]  R. Freitas.  Nanotechnology, nanomedicine and nanosurgery. , 2005, International journal of surgery.

[11]  V. Torchilin.  Recent advances with liposomes as pharmaceutical carriers , 2005, Nature Reviews Drug Discovery.

[12]  Ayusman Sen,et al.  Biomimetic behavior of synthetic particles: from microscopic randomness to macroscopic control. , 2010, Physical chemistry chemical physics : PCCP.

[13]  Ayusman Sen,et al.  Catalytic motors for transport of colloidal cargo. , 2008, Nano letters.

[14]  Geoffrey A Ozin,et al.  Synthetic self-propelled nanorotors. , 2005, Chemical communications.

[15]  Sirilak Sattayasamitsathit,et al.  Highly efficient catalytic microengines: template electrosynthesis of polyaniline/platinum microtubes. , 2011, Journal of the American Chemical Society.

[16]  Kristina Luthman,et al.  Theoretical Predictions of Drug Absorption in Drug Discovery and Development , 2002, Clinical pharmacokinetics.

[17]  Samuel Sanchez,et al.  Catalytic Janus motors on microfluidic chip: deterministic motion for targeted cargo delivery. , 2012, ACS nano.

[18]  Samuel Sanchez,et al.  Controlled manipulation of multiple cells using catalytic microbots. , 2011, Chemical communications.

[19]  Roland Stracke,et al.  Motor protein-driven unidirectional transport of micrometer-sized cargoes across isopolar microtubule arrays , 2001 .

[20]  Viola Vogel,et al.  Harnessing biological motors to engineer systems for nanoscale transport and assembly. , 2008, Nature nanotechnology.

[21]  H. Berg,et al.  Moving fluid with bacterial carpets. , 2004, Biophysical journal.

[22]  Yang Wang,et al.  Hydrazine fuels for bimetallic catalytic microfluidic pumping. , 2007, Journal of the American Chemical Society.

[23]  A. Dash,et al.  Therapeutic applications of implantable drug delivery systems. , 1998, Journal of pharmacological and toxicological methods.

[24]  O. Schmidt,et al.  Catalytic microtubular jet engines self-propelled by accumulated gas bubbles. , 2009, Small.

[25]  Satoshi Murakami,et al.  Crystal structure of bacterial multidrug efflux transporter AcrB , 2002, Nature.

[26]  Tad Hogg,et al.  Chemical Power for Microscopic Robots in Capillaries , 2009, Nanomedicine : nanotechnology, biology, and medicine.

[27]  Geoffrey A Ozin,et al.  Nanolocomotion - catalytic nanomotors and nanorotors. , 2010, Small.

[28]  Samudra Sengupta,et al.  Drop-off of colloidal cargo transported by catalytic Pt-Au nanomotors via photochemical stimuli. , 2010, Small.

[29]  Neetu Singh,et al.  Nanoparticles that communicate in vivo to amplify tumour targeting. , 2011, Nature materials.

[30]  O. Schmidt,et al.  Microbots swimming in the flowing streams of microfluidic channels. , 2011, Journal of the American Chemical Society.

[31]  F. Hirayama,et al.  Cyclodextrin Drug Carrier Systems. , 1998, Chemical reviews.

[32]  Oliver G. Schmidt,et al.  Rolled-up nanotech on polymers: from basic perception to self-propelled catalytic microengines. , 2011, Chemical Society reviews.

[33]  Yuichi Hiratsuka,et al.  A microrotary motor powered by bacteria , 2006, Proceedings of the National Academy of Sciences.

[34]  S. Balasubramanian,et al.  Chemical sensing based on catalytic nanomotors: motion-based detection of trace silver. , 2009, Journal of the American Chemical Society.

[35]  K. Kataoka,et al.  Block copolymer micelles for drug delivery: design, characterization and biological significance. , 2001, Advanced drug delivery reviews.

[36]  M. A. Northrup,et al.  Functional integration of PCR amplification and capillary electrophoresis in a microfabricated DNA analysis device. , 1996, Analytical chemistry.

[37]  E. Fullerton,et al.  Cargo-towing fuel-free magnetic nanoswimmers for targeted drug delivery. , 2012, Small.

[38]  S. Balasubramanian,et al.  Motion-based DNA detection using catalytic nanomotors. , 2010, Nature communications.

[39]  Asim Nisar,et al.  MEMS-based micropumps in drug delivery and biomedical applications , 2008 .

[40]  A. Walmsley,et al.  The structure and function of drug pumps: an update. , 2003, Trends in microbiology.

[41]  Susana Campuzano,et al.  Micromachine-enabled capture and isolation of cancer cells in complex media. , 2011, Angewandte Chemie.

[42]  Walter F Paxton,et al.  Motility of catalytic nanoparticles through self-generated forces. , 2005, Chemistry.

[43]  Vincent M Rotello,et al.  Colloidal microcapsules: self-assembly of nanoparticles at the liquid-liquid interface. , 2010, Chemistry, an Asian journal.

[44]  Susana Campuzano,et al.  Ternary surface monolayers for ultrasensitive (zeptomole) amperometric detection of nucleic acid hybridization without signal amplification. , 2010, Analytical chemistry.

[45]  Michael E Ibele,et al.  Emergent, collective oscillations of self-mobile particles and patterned surfaces under redox conditions. , 2010, ACS nano.

[46]  Sirilak Sattayasamitsathit,et al.  Rapid delivery of drug carriers propelled and navigated by catalytic nanoshuttles. , 2010, Small.

[47]  A R Walmsley,et al.  The structure and function of drug pumps. , 2001, Trends in microbiology.

[48]  Uwe Marx,et al.  Biological cardio-micro-pumps for microbioreactors and analytical micro-systems , 2011 .

[49]  S. Jacobson,et al.  Integrated system for rapid PCR-based DNA analysis in microfluidic devices. , 2000, Analytical chemistry.

[50]  T. Aida,et al.  Toward intelligent molecular machines: directed motions of biological and artificial molecules and assemblies. , 2005, Chemical reviews.

[51]  E. Purcell.  Life at Low Reynolds Number , 2008 .

[52]  Martin Pumera,et al.  Magnetic Control of Tubular Catalytic Microbots for the Transport, Assembly, and Delivery of Micro‐objects , 2010 .

[53]  Nathan Nelson,et al.  The emerging structure of vacuolar ATPases. , 2006, Physiology.

[54]  W. Xi,et al.  Self-propelled nanotools. , 2012, ACS nano.

[55]  B. Alberts.  The Cell as a Collection of Protein Machines: Preparing the Next Generation of Molecular Biologists , 1998, Cell.

[56]  R. J. Lee,et al.  Targeted drug delivery via the folate receptor. , 2000, Advanced drug delivery reviews.

[57]  S. T. Phillips,et al.  Self-powered microscale pumps based on analyte-initiated depolymerization reactions. , 2012, Angewandte Chemie.

[58]  Wei Gao,et al.  Nano/Microscale motors: biomedical opportunities and challenges. , 2012, ACS nano.

[59]  Yanyan Cao,et al.  Catalytic nanomotors: autonomous movement of striped nanorods. , 2004, Journal of the American Chemical Society.

[60]  Yang Wang,et al.  Catalytic micropumps: microscopic convective fluid flow and pattern formation. , 2005, Journal of the American Chemical Society.

[61]  Kazuhiko Kinosita,et al.  Direct observation of the rotation of F1-ATPase , 1997, Nature.

[62]  V. Vogel,et al.  Molecular shuttles based on motor proteins: active transport in synthetic environments. , 2001, Journal of biotechnology.

[63]  Zuzanna S Siwy,et al.  Learning Nature's Way: Biosensing with Synthetic Nanopores , 2007, Science.

[64]  Samudra Sengupta,et al.  Substrate catalysis enhances single-enzyme diffusion. , 2010, Journal of the American Chemical Society.

[65]  Cees Dekker,et al.  Motor Proteins at Work for Nanotechnology , 2007, Science.

[66]  Krzysztof K. Krawczyk,et al.  Magnetic Helical Micromachines: Fabrication, Controlled Swimming, and Cargo Transport , 2012, Advanced materials.

[67]  Joseph Wang,et al.  Cargo-towing synthetic nanomachines: towards active transport in microchip devices. , 2012, Lab on a chip.

[68]  Filiz Kuralay,et al.  Functionalized micromachines for selective and rapid isolation of nucleic acid targets from complex samples. , 2011, Nano letters.

[69]  Ayusman Sen,et al.  Light‐Driven Titanium‐Dioxide‐Based Reversible Microfireworks and Micromotor/Micropump Systems , 2010 .

[70]  Russell J. Stewart,et al.  Polarized Alignment and Surface Immobilization of Microtubules for Kinesin-Powered Nanodevices , 2001 .

[71]  Susana Campuzano,et al.  Bacterial isolation by lectin-modified microengines. , 2012, Nano letters.

[72]  M. Putman,et al.  Molecular Properties of Bacterial Multidrug Transporters , 2000, Microbiology and Molecular Biology Reviews.

[73]  Q. Pankhurst,et al.  Applications of magnetic nanoparticles in biomedicine , 2003 .

[74]  S C Jakeway,et al.  Miniaturized total analysis systems for biological analysis , 2000, Fresenius' journal of analytical chemistry.

[75]  Ioannis K. Kaliakatsos,et al.  Microrobots for minimally invasive medicine. , 2010, Annual review of biomedical engineering.

[76]  T. Kenny,et al.  Measurements and modeling of two-phase flow in microchannels with nearly constant heat flux boundary conditions , 2002 .

[77]  Juan G. Santiago,et al.  A review of micropumps , 2004 .

[78]  G. Ozin,et al.  Fuel for thought: chemically powered nanomotors out-swim nature's flagellated bacteria. , 2010, ACS nano.

[79]  Stephen J. Ebbens,et al.  In pursuit of propulsion at the nanoscale , 2010 .

[80]  Albert van den Berg,et al.  A silicon integrated miniature chemical analysis system , 1992 .

[81]  Kazushi Ishiyama,et al.  Magnetic micromachines for medical applications , 2002 .