Surface chemistry governs cellular tropism of nanoparticles in the brain

Eric Song, Alice Gaudin, Amanda R. King, Young-Eun Seo, Hee-Won Suh, Yang Deng, Jiajia Cui, Gregory T. Tietjen, Anita Huttner and W. Mark Saltzman ()
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Eric Song: Malone Engineering Center, Yale University
Alice Gaudin: Malone Engineering Center, Yale University
Amanda R. King: Malone Engineering Center, Yale University
Young-Eun Seo: Malone Engineering Center, Yale University
Hee-Won Suh: Malone Engineering Center, Yale University
Yang Deng: Malone Engineering Center, Yale University
Jiajia Cui: Malone Engineering Center, Yale University
Gregory T. Tietjen: Malone Engineering Center, Yale University
Anita Huttner: Yale University
W. Mark Saltzman: Malone Engineering Center, Yale University

Nature Communications, 2017, vol. 8, issue 1, 1-14

Abstract: Abstract Nanoparticles are of long-standing interest for the treatment of neurological diseases such as glioblastoma. Most past work focused on methods to introduce nanoparticles into the brain, suggesting that reaching the brain interstitium will be sufficient to ensure therapeutic efficacy. However, optimized nanoparticle design for drug delivery to the central nervous system is limited by our understanding of their cellular deposition in the brain. Here, we investigated the cellular fate of poly(lactic acid) nanoparticles presenting different surface chemistries, after administration by convection-enhanced delivery. We demonstrate that nanoparticles with ‘stealth’ properties mostly avoid internalization by all cell types, but internalization can be enhanced by functionalization with bio-adhesive end-groups. We also show that association rates measured in cultured cells predict the extent of internalization of nanoparticles in cell populations. Finally, evaluating therapeutic efficacy in an orthotopic model of glioblastoma highlights the need to balance significant uptake without inducing adverse toxicity.

Date: 2017
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DOI: 10.1038/ncomms15322

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