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Nanoparticle-modified microrobots for in vivo antibiotic delivery to treat acute bacterial pneumonia


Bioinspired microrobots capable of actively moving in biological fluids have attracted considerable attention for biomedical applications because of their unique dynamic features that are otherwise difficult to achieve by their static counterparts. Here we use click chemistry to attach antibiotic-loaded neutrophil membrane-coated polymeric nanoparticles to natural microalgae, thus creating hybrid microrobots for the active delivery of antibiotics in the lungs in vivo. The microrobots show fast speed (>110 µm s−1) in simulated lung fluid and uniform distribution into deep lung tissues, low clearance by alveolar macrophages and superb tissue retention time (>2 days) after intratracheal administration to test animals. In a mouse model of acute Pseudomonas aeruginosa pneumonia, the microrobots effectively reduce bacterial burden and substantially lessen animal mortality, with negligible toxicity. Overall, these findings highlight the attractive functions of algae–nanoparticle hybrid microrobots for the active in vivo delivery of therapeutics to the lungs in intensive care unit settings.

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Fig. 1: Preparation and structural characterization of the algae–nanoparticle hybrid microrobot (denoted as ‘algae-NP-robot’).
Fig. 2: Motion behaviour of algae-NP-robot.
Fig. 3: Lung distribution of algae-NP-robot.
Fig. 4: In vivo therapeutic efficacy of algae-NP-robot.
Fig. 5: In vivo safety evaluation of algae-NP(Cip)-robot.

Data availability

The data supporting the findings of this study are available within the paper, its Supplementary Information files and from the corresponding authors upon reasonable request. Source data are provided with this paper.


  1. Li, J. et al. Micro/nanorobots for biomedicine: delivery, surgery, sensing, and detoxification. Sci. Robot. 2, eaam6431 (2017).

    Google Scholar 

  2. Gao, C. et al. Biomedical micro‐/nanomotors: from overcoming biological barriers to in vivo imaging. Adv. Mater. 33, 2000512 (2020).

  3. Wu, Z., Chen, Y., Mukasa, D., Pak, O. S. & Gao, W. Medical micro/nanorobots in complex media. Chem. Soc. Rev. 49, 8088–8112 (2020).

    CAS  Google Scholar 

  4. Esteban-Fernández de Ávila, B. et al. Micromotor-enabled active drug delivery for in vivo treatment of stomach infection. Nat. Commun. 8, 272 (2017).

    Google Scholar 

  5. Wu, Z. et al. A microrobotic system guided by photoacoustic computed tomography for targeted navigation in intestines in vivo. Sci. Robot. 4, eaax0613 (2019).

    Google Scholar 

  6. Wu, Z. et al. A swarm of slippery micropropellers penetrates the vitreous body of the eye. Sci. Adv. 4, eaat4388 (2018).

    CAS  Google Scholar 

  7. Gao, W. et al. Artificial micromotors in the mouse’s stomach: a step toward in vivo use of synthetic motors. ACS Nano 9, 117–123 (2015).

    CAS  Google Scholar 

  8. Wei, X. et al. Biomimetic micromotor enables active delivery of antigens for oral vaccination. Nano Lett. 19, 1914–1921 (2019).

    CAS  Google Scholar 

  9. Servant, A., Qiu, F., Mazza, M., Kostarelos, K. & Nelson, B. J. Controlled in vivo swimming of a swarm of bacteria-like microrobotic flagella. Adv. Mater. 27, 2981 (2015).

    CAS  Google Scholar 

  10. Yan, X. et al. Multifunctional biohybrid magnetite microrobots for imaging-guided therapy. Sci. Robot. 2, eaaq1155 (2017).

    Google Scholar 

  11. Sun, L. et al. Biohybrid robotics with living cell actuation. Chem. Soc. Rev. 49, 4043–4069 (2020).

    CAS  Google Scholar 

  12. Ricotti, L. et al. Biohybrid actuators for robotics: a review of devices actuated by living cells. Sci. Robot. 2, eaaq0459 (2017).

    Google Scholar 

  13. Felfoul, O. et al. Magneto-aerotactic bacteria deliver drug-containing nanoliposomes to tumour hypoxic regions. Nat. Nanotechnol. 11, 941–947 (2016).

    CAS  Google Scholar 

  14. Medina-Sánchez, M., Schwarz, L., Meyer, A. K., Hebenstreit, F. & Schmidt, O. G. Cellular cargo delivery: toward assisted fertilization by sperm carrying micromotors. Nano Lett. 16, 555–561 (2015).

    Google Scholar 

  15. Weibel, D. B. et al. Microoxen: microorganisms to move microscale loads. Proc. Natl Acad. Sci. USA 102, 11963–11967 (2005).

    Google Scholar 

  16. Yasa, O., Erkoc, P., Alapan, Y. & Sitti, M. Microalga-powered microswimmers toward active cargo delivery. Adv. Mater. 30, 1804130 (2018).

    Google Scholar 

  17. Silflow, C. D. & Lefebvre, P. A. Assembly and motility of eukaryotic cilia and flagella. Lessons from Chlamydomonas reinhardtii. Plant Physiol. 127, 1500–1507 (2001).

    CAS  Google Scholar 

  18. Zhang, Q. et al. Neutrophil membrane-coated nanoparticles inhibit synovial inflammation and alleviate joint damage in inflammatory arthritis. Nat. Nanotechnol. 13, 1182–1190 (2018).

    Google Scholar 

  19. Metersky, M. L. & Kalil, A. C. Management of ventilator-associated pneumonia: guidelines. Clin. Chest Med. 39, 797–808 (2018).

    Google Scholar 

  20. Schreiber, M. P. & Shorr, A. F. Challenges and opportunities in the treatment of ventilator-associated pneumonia. Expert Rev. Anti Infec. Ther. 15, 23–32 (2017).

    CAS  Google Scholar 

  21. Muscedere, J. et al. The clinical impact and preventability of ventilator-associated conditions in critically ill patients who are mechanically ventilated. Chest 144, 1453–1460 (2013).

    Google Scholar 

  22. Melsen, W. G. et al. Attributable mortality of ventilator-associated pneumonia: a meta-analysis of individual patient data from randomised prevention studies. Lancet Infect. Dis. 13, 665–671 (2013).

    Google Scholar 

  23. Kharel, S., Bist, A. & Mishra, S. K. Ventilator-associated pneumonia among ICU patients in WHO Southeast Asian region: a systematic review. PLoS ONE 16, e0247832 (2021).

    CAS  Google Scholar 

  24. Vincent, J.-L., de Souza Barros, D. & Cianferoni, S. Diagnosis, management and prevention of ventilator-associated pneumonia. Drugs 70, 1927–1944 (2010).

    Google Scholar 

  25. Kerschgens, I. P. & Gademann, K. Antibiotic algae by chemical surface engineering. ChemBioChem 19, 439–443 (2018).

    CAS  Google Scholar 

  26. Szponarski, M. et al. On-cell catalysis by surface engineering of live cells with an artificial metalloenzyme. Commun. Chem. 1, 84 (2018).

    Google Scholar 

  27. Shi, P. et al. Spatiotemporal control of cell–cell reversible interactions using molecular engineering. Nat. Commun. 7, 13088 (2016).

    CAS  Google Scholar 

  28. Wang, H. et al. Metabolic labeling and targeted modulation of dendritic cells. Nat. Mater. 19, 1244–1252 (2020).

    CAS  Google Scholar 

  29. Hu, Q. et al. Conjugation of haematopoietic stem cells and platelets decorated with anti-PD-1 antibodies augments anti-leukaemia efficacy. Nat. Biomed. Eng. 2, 831–840 (2018).

    Google Scholar 

  30. Fang, R. H. et al. Cell membrane coating nanotechnology. Adv. Mater. 30, 1706759 (2018).

    Google Scholar 

  31. Kumar, A. et al. A biocompatible synthetic lung fluid based on human respiratory tract lining fluid composition. Pharm. Res. 34, 2454–2465 (2017).

    CAS  Google Scholar 

  32. Tanaka, Y. et al. Acclimation of the photosynthetic machinery to high temperature in Chlamydomonas reinhardtii requires synthesis de novo of proteins encoded by the nuclear and chloroplast genomes. Plant Physiol. 124, 441–449 (2000).

    CAS  Google Scholar 

  33. Singh, S. P. & Singh, P. Effect of temperature and light on the growth of algae species: a review. Renew. Sust. Energ. Rev. 50, 431–444 (2015).

    CAS  Google Scholar 

  34. Ortiz-Munoz, G. & Looney, M. R. Non-invasive intratracheal instillation in mice. Bio-protocol 5, e1504 (2015).

    Google Scholar 

  35. Sibille, Y. & Reynolds, H. Y. Macrophages and polymorphonuclear neutrophils in lung defense and injury. Am. Rev. Respir. Dis. 141, 471–501 (1990).

    CAS  Google Scholar 

  36. Justo, J. A., Danziger, L. H. & Gotfried, M. H. Efficacy of inhaled ciprofloxacin in the management of non-cystic fibrosis bronchiectasis. Ther. Adv. Respir. Dis. 7, 272–287 (2013).

    Google Scholar 

  37. Oliver, A. et al. Hypermutation and the preexistence of antibiotic-resistant Pseudomonas aeruginosa mutants: implications for susceptibility testing and treatment of chronic infections. Antimicrob. Agents Chemother. 48, 4226–4233 (2004).

    Google Scholar 

  38. Lovewell, R. R., Patankar, Y. R. & Berwin, B. Mechanisms of phagocytosis and host clearance of Pseudomonas aeruginosa. Am. J. Physiol. Lung Cell. Mol. Physiol. 306, L591–L603 (2014).

    CAS  Google Scholar 

  39. Hayashi, F. et al. The innate immune response to bacterial flagellin is mediated by Toll-like receptor 5. Nature 410, 1099–1103 (2001).

    Google Scholar 

  40. Boyden, E. et al. Millisecond-timescale, genetically targeted optical control of neural activity. Nat. Neurosci. 8, 1263–1268 (2005).

    CAS  Google Scholar 

  41. Sineshchekov, O. A., Jung, K.-H. & Spudich, J. L. Two rhodopsins mediate phototaxis to low- and high-intensity light in Chlamydomonas reinhardtii. Proc. Natl Acad. Sci. USA 99, 8689–8694 (2002).

    CAS  Google Scholar 

  42. Akolpoglu, M. B. et al. High‐yield production of biohybrid microalgae for on‐demand cargo delivery. Adv. Sci. 7, 2001256 (2020).

    CAS  Google Scholar 

  43. Delalat, B. et al. Targeted drug delivery using genetically engineered diatom biosilica. Nat. Commun. 6, 8791 (2015).

    CAS  Google Scholar 

  44. Martel, S. et al. Flagellated magnetotactic bacteria as controlled MRI-trackable propulsion and steering systems for medical nanorobots operating in the human microvasculature. Int. J. Robot. Res. 28, 571–582 (2009).

    Google Scholar 

  45. Zhang, Y. et al. A bioadhesive nanoparticle–hydrogel hybrid system for localized antimicrobial drug delivery. ACS Appl. Mater. Interfaces 8, 18367–18374 (2016).

    Google Scholar 

  46. Sato, M., Murata, Y., Mizusawa, M., Iwahashi, H. & Oka, S.-I. A simple and rapid dual fluorescence viability assay for microalgae. Microbiol. Cult. Coll. 20, 53–59 (2004).

    Google Scholar 

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This work is supported by the National Institutes of Health under award no. R01CA200574 (L.Z.).

Author information

Authors and Affiliations



F.Z., J. Zhuang, L.Z. and J.W. conceived the study and designed the experiments. F.Z., J. Zhuang, Z.L. and H.G. conducted the experiments. F.Z., J. Zhuang, Z.L., H.G., B.E.-F.Á., Y.D., Q.Z., J. Zhou, L.Y., E.K., R.H.F., L.Z. and J.W. analysed the data. F.Z., J. Zhuang, Z.L., H.G., B.E.-F.Á., W.G., V.N., R.H.F., L.Z. and J.W. wrote the manuscript. All the authors reviewed, edited and approved the paper.

Corresponding authors

Correspondence to Liangfang Zhang or Joseph Wang.

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Nature Materials thanks Kelly Bachta, Sylvain Martel, Bradley Nelson and the other, anonymous, reviewer(s) for their contribution to the peer review of this work.

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Supplementary information

Supplementary Information

Supplementary Figs. 1–20, Table 1, captions for Videos 1–5 and references.

Reporting Summary

Supplementary Video 1

Motion comparison of bare algae with algae-NP-robot in SLF at BT (37 °C) at different operation times (0, 15 and 60 min).

Supplementary Video 2

Representative 2 s tracking of algae-NP-robot in SLF at BT (37 °C) at different operation times (0, 15 and 60 min).

Supplementary Video 3

Motion of algae-NP-robot when co-cultured with macrophage.

Supplementary Video 4

Motion of algae-NP-robot in SLF at BT (37 °C) in the dark at various timepoints (12, 24 and 48 h).

Supplementary Video 5

Random motion and phototaxis of algae-NP-robot under an external light source.

Supplementary Data 1

Source data for Supplementary Figs. 1–20.

Source data

Source Data for Figs. 2–5

One file for each relevant figure, containing all the source data.

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Zhang, F., Zhuang, J., Li, Z. et al. Nanoparticle-modified microrobots for in vivo antibiotic delivery to treat acute bacterial pneumonia. Nat. Mater. 21, 1324–1332 (2022).

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