Surface chemistry governs cellular tropism of nanoparticles in the brain

Nature Communications
Eric SongW Mark Saltzman

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.

References

Jan 1, 1995·Journal of Neuro-oncology·A T AasL G Salford
Mar 15, 1994·Proceedings of the National Academy of Sciences of the United States of America·R H BoboE H Oldfield
Sep 1, 1996·Acta Neuropathologica·W RoggendorfW Paulus
Mar 4, 2003·Nature Reviews. Drug Discovery·J Milton Harris, Robert B Chess
Feb 18, 2005·NeuroRx : the Journal of the American Society for Experimental NeuroTherapeutics·William M Pardridge
Mar 2, 2005·Nature Reviews. Cancer·Mauro Ferrari
May 26, 2005·Pharmacological Reviews·Brian T Hawkins, Thomas P Davis
Jan 3, 2007·Drug Discovery Today·William M Pardridge
Jan 16, 2007·Cancer Cell·Christopher CalabreseRichard J Gilbertson
Apr 17, 2007·Nature Neuroscience·Makiko NagaiSerge Przedborski
Aug 2, 2008·The New England Journal of Medicine·Patrick Y Wen, Santosh Kesari
Jun 22, 2011·Drug Delivery and Translational Research·Andrew J SawyerW Mark Saltzman
Aug 5, 2011·Journal of Neurochemistry·Robert SpoelgenArmin Schneider
Sep 14, 2011·Journal of Neuroscience Methods·Danielle Guez-BarberBruce T Hope
Dec 24, 2011·Journal of the American Chemical Society·Carl D WalkeyWarren C W Chan
Aug 31, 2012·Expert Opinion on Drug Delivery·Ricardo P GarayPascal Richette
Aug 31, 2012·Science Translational Medicine·Elizabeth A NanceJustin Hanes
Jan 11, 2013·Journal of the American Chemical Society·Anna LesniakChristoffer Åberg
Jun 26, 2013·Pharmaceutical Research·Huile GaoXinguo Jiang
Jul 3, 2013·Proceedings of the National Academy of Sciences of the United States of America·Jiangbing ZhouW Mark Saltzman
Aug 29, 2013·Advanced Drug Delivery Reviews·Jörg Kreuter
Jan 20, 2015·Nature Reviews. Drug Discovery·Christopher J ChengW Mark Saltzman
Mar 13, 2015·Advanced Healthcare Materials·Panagiotis MastorakosJustin Hanes
Sep 29, 2015·Nature Materials·Yang DengW Mark Saltzman
Oct 11, 2015·Journal of Drug Targeting·Jennifer K Saucier-SawyerW Mark Saltzman
Oct 24, 2015·Tumour Biology : the Journal of the International Society for Oncodevelopmental Biology and Medicine·Amanda L PlaconePeter C Searson
Nov 20, 2015·Science Translational Medicine·Miles A MillerRalph Weissleder
Jan 17, 2016·Journal of Controlled Release : Official Journal of the Controlled Release Society·Chayanon NgambenjawongSuzie H Pun
Mar 11, 2016·Nanomedicine : Nanotechnology, Biology, and Medicine·Jin-Kyu ParkYasuko Iwakiri
Apr 12, 2016·Journal of Controlled Release : Official Journal of the Controlled Release Society·Jennifer K Saucier-SawyerW Mark Saltzman
Sep 22, 2016·Proceedings of the National Academy of Sciences of the United States of America·Tsuguhide TakeshimaRaquibul Hannan
Sep 25, 2016·Proceedings of the National Academy of Sciences of the United States of America·Yang DengW Mark Saltzman

❮ Previous
Next ❯

Citations

Aug 10, 2018·Small·Mónica Giménez-MarquésPatricia Horcajada
May 16, 2019·Chemical Society Reviews·Wei TangXiaoyuan Chen
Jun 28, 2018·Nature Communications·Adele S RicciardiW Mark Saltzman
Jul 12, 2018·Nature Communications·Jacob S BrennerVladimir Muzykantov
Oct 22, 2019·Therapeutic Advances in Medical Oncology·Shih-Jung LiuYuan-Yun Tseng
Feb 19, 2019·Frontiers in Immunology·Bengt Fadeel
May 6, 2020·Drug Delivery and Translational Research·Yunho Han, Ji-Ho Park
Jan 27, 2019·Bioengineering & Translational Medicine·Hee-Won SuhMichael Girardi
Jan 24, 2021·Acta Biomaterialia·Sarah J UllrichDavid H Stitelman
Jun 26, 2020·Molecular Pharmaceutics·Rebecca M KandellEster J Kwon
Feb 3, 2021·Proceedings of the National Academy of Sciences of the United States of America·Jamie K HuMichael Girardi
Apr 13, 2019·Journal of Controlled Release : Official Journal of the Controlled Release Society·Karina NegronJung Soo Suk
May 18, 2021·Matter·Xiuying LiZhenpeng Qin
Aug 24, 2021·Advanced Science·Meng ZhengBingyang Shi
Sep 21, 2017·Computerized Medical Imaging and Graphics : the Official Journal of the Computerized Medical Imaging Society·David Lei ChiW Mark Saltzman
Nov 30, 2021·Journal of Materials Chemistry. B, Materials for Biology and Medicine·Chuangli ZhangPengfei Wang

❮ Previous
Next ❯

Methods Mentioned

BETA
dynamic light scattering
flow cytometry
fluorescence-activated cell sorting
confocal microscopy
nanoprecipitation
flow
Fluorescence

Software Mentioned

Adobe Photoshop
FlowJo
Excel
MATLAB
Prism
ImageJ

Related Concepts

Trending Feeds

COVID-19

Coronaviruses encompass a large family of viruses that cause the common cold as well as more serious diseases, such as the ongoing outbreak of coronavirus disease 2019 (COVID-19; formally known as 2019-nCoV). Coronaviruses can spread from animals to humans; symptoms include fever, cough, shortness of breath, and breathing difficulties; in more severe cases, infection can lead to death. This feed covers recent research on COVID-19.

Blastomycosis

Blastomycosis fungal infections spread through inhaling Blastomyces dermatitidis spores. Discover the latest research on blastomycosis fungal infections here.

Nuclear Pore Complex in ALS/FTD

Alterations in nucleocytoplasmic transport, controlled by the nuclear pore complex, may be involved in the pathomechanism underlying multiple neurodegenerative diseases including Amyotrophic Lateral Sclerosis and Frontotemporal Dementia. Here is the latest research on the nuclear pore complex in ALS and FTD.

Applications of Molecular Barcoding

The concept of molecular barcoding is that each original DNA or RNA molecule is attached to a unique sequence barcode. Sequence reads having different barcodes represent different original molecules, while sequence reads having the same barcode are results of PCR duplication from one original molecule. Discover the latest research on molecular barcoding here.

Chronic Fatigue Syndrome

Chronic fatigue syndrome is a disease characterized by unexplained disabling fatigue; the pathology of which is incompletely understood. Discover the latest research on chronic fatigue syndrome here.

Evolution of Pluripotency

Pluripotency refers to the ability of a cell to develop into three primary germ cell layers of the embryo. This feed focuses on the mechanisms that underlie the evolution of pluripotency. Here is the latest research.

Position Effect Variegation

Position Effect Variagation occurs when a gene is inactivated due to its positioning near heterochromatic regions within a chromosome. Discover the latest research on Position Effect Variagation here.

STING Receptor Agonists

Stimulator of IFN genes (STING) are a group of transmembrane proteins that are involved in the induction of type I interferon that is important in the innate immune response. The stimulation of STING has been an active area of research in the treatment of cancer and infectious diseases. Here is the latest research on STING receptor agonists.

Microbicide

Microbicides are products that can be applied to vaginal or rectal mucosal surfaces with the goal of preventing, or at least significantly reducing, the transmission of sexually transmitted infections. Here is the latest research on microbicides.