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Macrophages as Targets and Mediators in the Transport of Nanotherapeutics

34 Pages Posted: 19 Jun 2019 Publication Status: Review Complete

See all articles by Stefan Franco

Stefan Franco

University of New Mexico - Department of Internal Medicine

Achraf Noureddine

University of New Mexico - Center for Micro-Engineered Materials (CMEM)

Michael Paffett

University of New Mexico

C. Jeffrey Brinker

University of New Mexico - Center for Micro-Engineered Materials (CMEM)

Natalie Adolphi

University of New Mexico

Rita Elena Serda

University of New Mexico - Department of Internal Medicine

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Abstract

Macrophages line the walls of microvasculature, extending processes into the blood flow to capture intruders, including nanoparticles. Here, using mesoporous silica or silicon particles, we show the interplay between macrophages and nanomaterial from initial uptake to intracellular trafficking along microtubules, to intercellular trafficking of material to neighboring cells. Transfer of materials between cells includes robust transfer of nanoparticles and cargo from macrophages to cancer cells in cytoplasmic bridges, coined tunneling nanotubes (TNT), and in thick, adherent connections with elaborate points of connection between cells. Both direct administration of nanoparticles and adoptive transfer of nanoparticle-loaded splenocytes in mice results in abundant localization of nanomaterials within macrophages 24 hours post injection. The relevance of macrophages as natural targets of nanomaterials and as significant regulators of the tumor microenvironment arises as an overlooked key-consideration when designing nano therapeutics for optimal drug delivery and therapeutic benefit.

Keywords: macrophage, doxorubicin, cancer, intercellular transport, mesoporous silica or silicon particle, tunneling nanotubes

Suggested Citation

Franco, Stefan and Noureddine, Achraf and Paffett, Michael and Brinker, C. Jeffrey and Adolphi, Natalie and Serda, Rita Elena, Macrophages as Targets and Mediators in the Transport of Nanotherapeutics (June 19, 2019). Available at SSRN: https://ssrn.com/abstract=3406386 or http://dx.doi.org/10.2139/ssrn.3406386
This version of the paper has not been formally peer reviewed.

Stefan Franco

University of New Mexico - Department of Internal Medicine

Albuquerque, NM 87131-0001
United States

Achraf Noureddine

University of New Mexico - Center for Micro-Engineered Materials (CMEM) ( email )

Albuquerque, NM 87131-1221
United States

Michael Paffett

University of New Mexico

107 Humanitites Building
Albuquerque, NM 87131-1221
United States

C. Jeffrey Brinker

University of New Mexico - Center for Micro-Engineered Materials (CMEM)

Albuquerque, NM 87131-1221
United States

Natalie Adolphi

University of New Mexico

107 Humanitites Building
Albuquerque, NM 87131-1221
United States

Rita Elena Serda (Contact Author)

University of New Mexico - Department of Internal Medicine ( email )

Albuquerque, NM 87131-0001
United States

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