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Synthetic nanoparticles functionalized with biomimetic leukocyte membranes possess cell-like functions

Nature Nanotechnology volume 8, pages 61–68 (2013)Cite this article

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Abstract

The therapeutic efficacy of systemic drug-delivery vehicles depends on their ability to evade the immune system, cross the biological barriers of the body and localize at target tissues. White blood cells of the immune system—known as leukocytes—possess all of these properties and exert their targeting ability through cellular membrane interactions. Here, we show that nanoporous silicon particles can successfully perform all these actions when they are coated with cellular membranes purified from leukocytes. These hybrid particles, called leukolike vectors, can avoid being cleared by the immune system. Furthermore, they can communicate with endothelial cells through receptor–ligand interactions, and transport and release a payload across an inflamed reconstructed endothelium. Moreover, leukolike vectors retained their functions when injected in vivo, showing enhanced circulation time and improved accumulation in a tumour.

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Figure 1: The leukolike vector.
Figure 2: Inhibition of particle opsonization and phagocytosis.
Figure 3: Particle adhesion to healthy and inflamed endothelium.
Figure 4: LLV effect on endothelial barrier function.
Figure 5: Enhanced tumoritropic accumulation in mice.

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Acknowledgements

The authors acknowledge support from the Alliance for NanoHealth Department of Defence Telemedicine & Advanced Technology Research Center (09-W81XWH-10-2-0125), the Defense Advanced Research Projects Agency (W911NF-11-1-0266), the National Institutes of Health (U54CA143837 and U54CA151668), the Department of Defense/Breast Cancer Research Program (W81XWH-09-1-0212) and by The Methodist Hospital Research Institute including Ernest Cockrell Jr. Distinguished Endowed Chair. A.P. was supported by the Bianca Garavaglia Association (Italy). N.Q. was supported by the Ministero Istruzione Universita Ricerca (Italy). J.O.M. was supported by the National Institutes of Health Center for Clinical and Translational Sciences through Clinical and Translational Award TL1 RR024147 from the National Center for Research Resources. M.V.E. was supported by Euroclone S.p.a. The content of this Article is solely the responsibility of the authors and does not necessarily represent the official views of the National Center for Research Resources or the National Institutes of Health. The authors also thank M.E. Masserini, M. Agostini, D. Nitti and F. Hussain for their mentoring role, X. Liu for fabrication of the nanoporous silicon particles, K. Dunner Jr for assistance with transmission electron microscopy, K. Cui and The Methodist Hospital Research Institute Advanced Cellular and Tissue Microscope Core Facility for time-lapse live cell microscopy, D. Haviland and The Methodist Hospital Research Institute Flow Cytometry Core Facility and E. De Rosa for data analysis, N. Warier, S. Scaria, G. Adriani, P. Decuzzi, E.V. Zabre and A. Grattoni for technical support and M.G. Landry for graphical assistance.

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Author notes

  1. Ciro Chiappini

    Present address: Present address: Department of Materials, Imperial College London, South Kensington Campus, London SW7 2AZ, UK,

  2. Alessandro Parodi and Nicoletta Quattrocchi: These authors contributed equally to this work

Authors and Affiliations

  1. Department of Nanomedicine, The Methodist Hospital System Research Institute, Houston, 77030, Texas, USA

    Alessandro Parodi, Nicoletta Quattrocchi, Anne L. van de Ven, Ciro Chiappini, Michael Evangelopoulos, Jonathan O. Martinez, Brandon S. Brown, Sm Z. Khaled, Iman K. Yazdi, Maria Vittoria Enzo, Lucas Isenhart, Mauro Ferrari & Ennio Tasciotti

  2. Department of Experimental Oncology and Molecular Medicine, Fondazione IRCCS Istituto Nazionale Tumori, Milan, 20133, Italy

    Alessandro Parodi

  3. Department of Experimental Medicine, University of Milano Bicocca, Milan, 20052, Italy

    Nicoletta Quattrocchi

  4. The University of Texas Health Science Center at Houston, Houston, 77030, Texas, USA

    Jonathan O. Martinez & Brandon S. Brown

  5. Department of Biomedical Engineering, University of Houston, Houston, 77204, Texas, USA

    Iman K. Yazdi

  6. Department of Oncological and Surgical Sciences, 2nd Surgical Clinic, University of Padua, Padua, 35128, Italy

    Maria Vittoria Enzo

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Contributions

A.P. supervised all cellular experiments, interpreted the data and wrote the manuscript. N.Q. developed and optimized the protocols for leukolike vector assembly. A.V. designed and performed all intravital microscopy experiments and analysis and wrote the paper. C.C. manufactured the NPS. M.E. optimized the development of the system. J.O.M. carried out and analysed time-lapse microscopy experiments. B.B. performed confocal microscopy and flow cytometry. S.K. performed the physical and chemical characterization. I.K.Y. performed SEM and assisted with analysis. M.V.E. performed the transwell assays. L.I. optimized in vitro flow systems. M.F. performed the final edits of the manuscript and mentored the authors during the development of the project. E.T. conceived the LLV concept, wrote the paper and was the principal investigator of the major supporting grants.

Corresponding author

Correspondence to Ennio Tasciotti.

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Competing interests

Commercialization rights on the intellectual property presented in this paper have been acquired by Leonardo Biosystems, from the title holder, the University of Texas Health Science Center in Houston. M.F. is the founding scientist of Leonardo Biosystems, E.T. is the inventor of the technology and hereby both authors disclose potential financial interests.

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Parodi, A., Quattrocchi, N., van de Ven, A. et al. Synthetic nanoparticles functionalized with biomimetic leukocyte membranes possess cell-like functions. Nature Nanotech 8, 61–68 (2013). https://doi.org/10.1038/nnano.2012.212

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