Microalga‐Powered Microswimmers toward Active Cargo Delivery

Nature presents intriguing biological swimmers with innate energy harvesting abilities from their local environments. Use of natural swimmers as cargo delivery agents presents an alternative strategy to transport therapeutics inside the body to locations otherwise difficult to access by traditional delivery strategies. Herein, a biocompatible biohybrid microswimmer powered by a unicellular freshwater green microalga, Chlamydomonas reinhardtii, is reported. Polyelectrolyte-functionalized magnetic spherical cargoes (1 µm in diameter) are attached to surface of the microalgae via noncovalent interactions without the requirement for any chemical reaction. The 3D swimming motility of the constructed biohybrid algal microswimmers is characterized in the presence and absence of a uniform magnetic fields. In addition, motility of both microalgae and biohybrid algal microswimmers is investigated in various physiologically relevant conditions, including cell culture medium, human tubal fluid, plasma, and blood. Furthermore, it is demonstrated that the algal microswimmers are cytocompatible when co-cultured with healthy and cancerous cells. Finally, fluorescent isothiocyanate-dextran (a water-soluble polysaccharide) molecules are effectively delivered to mammalian cells using the biohybrid algal microswimmers as a proof-of-concept active cargo delivery demonstration. The microswimmer design described here presents a new class of biohybrid microswimmers with greater biocompatibility and motility for targeted delivery applications in medicine.

[1]  J. Arrieta,et al.  Phototaxis beyond turning: persistent accumulation and response acclimation of the microalga Chlamydomonas reinhardtii , 2016, Scientific Reports.

[2]  A. S. Mathuriya,et al.  Magnetotactic Bacteria: Performances and Challenges , 2015 .

[3]  S. Mayfield,et al.  Production of therapeutic proteins in algae, analysis of expression of seven human proteins in the chloroplast of Chlamydomonas reinhardtii. , 2010, Plant biotechnology journal.

[4]  J. Barnett,et al.  Advances in polyelectrolyte multilayer nanofilms as tunable drug delivery systems. , 2009, Nanotechnology, science and applications.

[5]  K. Bišová,et al.  Chlamydomonas reinhardtii: duration of its cell cycle and phases at growth rates affected by temperature , 2011, Planta.

[6]  I. Gruber,et al.  Embryo culture media for human IVF: which possibilities exist? , 2011, Journal of the Turkish German Gynecological Association.

[7]  P. Arratia,et al.  Flagellar Kinematics and Swimming of Algal Cells in Viscoelastic Fluids , 2015, Scientific Reports.

[8]  U. Gurkan,et al.  Microfluidic processing of synovial fluid for cytological analysis , 2017, Biomedical Microdevices.

[9]  Jennifer Sturgis,et al.  Bacteria-mediated delivery of nanoparticles and cargo into cells. , 2007, Nature nanotechnology.

[10]  R. Goldstein.  Green Algae as Model Organisms for Biological Fluid Dynamics. , 2014, Annual review of fluid mechanics.

[11]  S. Martel,et al.  Magneto-aerotactic bacteria deliver drug-containing nanoliposomes to tumour hypoxic regions , 2016, Nature nanotechnology.

[12]  Metin Sitti,et al.  Mobile microrobots for bioengineering applications. , 2017, Lab on a chip.

[13]  G. Whitesides,et al.  Microoxen: microorganisms to move microscale loads. , 2005, Proceedings of the National Academy of Sciences of the United States of America.

[14]  M. R. Edwards,et al.  Near and far-wall effects on the three-dimensional motion of bacteria-driven microbeads , 2013 .

[15]  J. Engbersen,et al.  Responsive layer-by-layer materials for drug delivery. , 2012, Journal of controlled release : official journal of the Controlled Release Society.

[16]  S. Martel,et al.  Covalent binding of nanoliposomes to the surface of magnetotactic bacteria for the synthesis of self-propelled therapeutic agents. , 2014, ACS nano.

[17]  G. Sauerbrey,et al.  Use of quartz vibration for weighing thin films on a microbalance , 1959 .

[18]  M. Sitti,et al.  Bioengineered and biohybrid bacteria-based systems for drug delivery. , 2016, Advanced drug delivery reviews.

[19]  Metin Sitti,et al.  Soft erythrocyte-based bacterial microswimmers for cargo delivery , 2018, Science Robotics.

[20]  Jiang Zhuang,et al.  Propulsion and Chemotaxis in Bacteria‐Driven Microswimmers , 2017, Advanced science.

[21]  S. Mayfield,et al.  The microalga Chlamydomonas reinhardtii as a platform for the production of human protein therapeutics , 2011, Bioengineered bugs.

[22]  Veronika Magdanz,et al.  Nano-and Micromotors Designed for Cancer Therapy , 2019, Molecules.

[23]  Yeonkyung Lee,et al.  New paradigm for tumor theranostic methodology using bacteria-based microrobot , 2013, Scientific Reports.

[24]  Lianqing Liu,et al.  Controlled regular locomotion of algae cell microrobots , 2016, Biomedical Microdevices.

[25]  Seong Young Ko,et al.  Active tumor-therapeutic liposomal bacteriobot combining a drug (paclitaxel)-encapsulated liposome with targeting bacteria (Salmonella Typhimurium) , 2016 .

[26]  Metin Sitti,et al.  Bio-hybrid cell-based actuators for microsystems. , 2014, Small.

[27]  Metin Sitti,et al.  Multifunctional Bacteria-Driven Microswimmers for Targeted Active Drug Delivery. , 2017, ACS nano.

[28]  Tim Bashford,et al.  Effect of wavelength and beam width on penetration in light-tissue interaction using computational methods , 2017, Lasers in Medical Science.

[29]  M. Sitti,et al.  Microemulsion-Based Soft Bacteria-Driven Microswimmers for Active Cargo Delivery. , 2017, ACS nano.

[30]  Metin Sitti,et al.  Bioadhesive Bacterial Microswimmers for Targeted Drug Delivery in the Urinary and Gastrointestinal Tracts , 2017, Advanced science.

[31]  Daniel Tam,et al.  Optimal feeding and swimming gaits of biflagellated organisms , 2011, Proceedings of the National Academy of Sciences.

[32]  R. Golestanian,et al.  A steering mechanism for phototaxis in Chlamydomonas , 2014, Journal of The Royal Society Interface.

[33]  Qi Zhou,et al.  Multifunctional biohybrid magnetite microrobots for imaging-guided therapy , 2017, Science Robotics.

[34]  P V Bayly,et al.  Propulsive forces on the flagellum during locomotion of Chlamydomonas reinhardtii. , 2011, Biophysical journal.

[35]  M. Polin,et al.  Entrainment dominates the interaction of microalgae with micron-sized objects , 2016, Nature Communications.

[36]  Changyou Chen,et al.  Construction and operation of a microrobot based on magnetotactic bacteria in a microfluidic chip. , 2012, Biomicrofluidics.

[37]  Sijia Wang,et al.  Electric-field–induced assembly and propulsion of chiral colloidal clusters , 2015, Proceedings of the National Academy of Sciences.

[38]  J. Gollub,et al.  Chlamydomonas Swims with Two “Gears” in a Eukaryotic Version of Run-and-Tumble Locomotion , 2009, Science.

[39]  Eric Diller,et al.  Biomedical Applications of Untethered Mobile Milli/Microrobots , 2015, Proceedings of the IEEE.

[40]  G. Sauerbrey.  Verwendung von Schwingquarzen zur Wägung dünner Schichten und zur Mikrowägung , 1959 .

[41]  Samuel Sanchez,et al.  Biohybrid Janus Motors Driven by Escherichia coli , 2016 .

[42]  Jake J. Abbott,et al.  How Should Microrobots Swim? , 2009 .

[43]  Metin Sitti,et al.  Magnetic steering control of multi-cellular bio-hybrid microswimmers. , 2014, Lab on a chip.

[44]  Sylvain Martel,et al.  Flagellated Magnetotactic Bacteria as Controlled MRI-trackable Propulsion and Steering Systems for Medical Nanorobots Operating in the Human Microvasculature , 2009, Int. J. Robotics Res..