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

Abstract

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.

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Acknowledgements

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

Author information

Authors and Affiliations

Authors

Contributions

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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The authors declare no competing interests.

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Peer review information

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. (2022). https://doi.org/10.1038/s41563-022-01360-9

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