Surface chemistry governs cellular tropism of nanoparticles in the brain
Citations Over TimeTop 10% of 2017 papers
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.
Related Papers
- → Large-Scale Screening Assay to Measure Epidermal Growth Factor Internalization(2000)12 cited
- → Role of carboxyl tail of the rat angiotensin II type 1A receptor in agonist-induced internalization of the receptor(1994)32 cited
- Antibody transport and internalization into tumours.(1990)
- → The Internalization and Therapeutic Activity of Antibody Drug Conjugates(2023)