Shape-directed compartmentalized delivery of a nanoparticle-conjugated small-molecule activator of an epigenetic enzyme in the brain

Journal of Controlled Release : Official Journal of the Controlled Release Society
Piyush ChaturbedyM Eswaramoorthy

Abstract

Targeted drug delivery to specific subcellular compartments of brain cells is challenging despite their importance in the treatment of several brain-related diseases. Herein, we report on shape-directed intracellular compartmentalization of nanoparticles in brain cells and their ability to deliver therapeutic molecules to specific organelles. Iron oxide (Fe3O4) nanoparticles with different morphologies (spheres, spindles, biconcaves, and nanotubes) were synthesized and coated with a fluorescent carbon layer derived from glucose (Fe3O4@C). In vivo studies showed that the Fe3O4@C nanoparticles with biconcave geometry localized predominantly in the nuclei of the brain cells, whereas those with nanotube geometry were contained mostly in the cytoplasm. Remarkably, a small-molecule activator of histone acetyltransferases delivered into the nuclei of the brain cells using nanoparticles with biconcave geometry showed enhancement in enzymatic activity by a factor of three and resulted in specific gene expression (transcription) compared with that of the molecule delivered to the cytoplasm using nanotube geometry.

References

Aug 1, 1995·Proceedings of the National Academy of Sciences of the United States of America·O BoussifJ P Behr
Feb 22, 2005·Advanced Drug Delivery Reviews·Bhawna GuptaVladimir P Torchilin
Sep 22, 2005·Bioconjugate Chemistry·Jesus M de la Fuente, Catherine C Berry
Mar 2, 2006·Pharmacological Reviews·Ikramy A KhalilHideyoshi Harashima
Jan 20, 2007·Biochemical Society Transactions·R Duncan
May 26, 2007·Angewandte Chemie·Peisheng XuYouqing Shen
Aug 9, 2007·Advanced Drug Delivery Reviews·Jaspreet K Vasir, Vinod Labhasetwar
Dec 5, 2008·Journal of the American Chemical Society·Chun-Jiang JiaJörg Raabe
Aug 25, 2009·Nature Neuroscience·Zhengliang GaoJenny Hsieh
Jan 1, 2010·Nature Reviews. Drug Discovery·Lawrence RajendranKai Simons
Jan 21, 2010·Journal of the American Chemical Society·Bin KangMostafa A El-Sayed
Jan 13, 2011·Pharmaceutical Research·Francisco C Pérez-MartínezValentín Ceña
May 10, 2011·Accounts of Chemical Research·Jin XieXiaoyuan Chen
Jun 15, 2011·Accounts of Chemical Research·Don HoShouheng Sun
Oct 11, 2011·Journal of the American Chemical Society·Lauren A AustinMostafa A El-Sayed
Oct 21, 2011·Bioconjugate Chemistry·Lauren A AustinMostafa A El-Sayed
Nov 22, 2011·Advanced Drug Delivery Reviews·Ho Lun WongReina Bendayan
Mar 27, 2012·Theranostics·Zhuang Liu, Xing-Jie Liang
Apr 25, 2012·Annual Review of Biomedical Engineering·Alexandre AlbaneseWarren C W Chan
Aug 4, 2012·Journal of Nanobiotechnology·Ruthrotha B SelviTapas K Kundu
Oct 13, 2012·Chemical Society Reviews·Kai YangZhuang Liu
Dec 6, 2012·Nature Nanotechnology·Marco P MonopoliKenneth A Dawson
Feb 14, 2013·ACS Nano·Heather HerdClaus-Michael Lehr
Feb 19, 2013·Current Opinion in Biotechnology·Yoram Cohen, Shani Yariv Shoushan
Jun 28, 2013·The Journal of Neuroscience : the Official Journal of the Society for Neuroscience·Snehajyoti ChatterjeeAnne-Laurence Boutillier
Jul 31, 2013·Drug Design, Development and Therapy·Niraj M Sakhrani, Harish Padh
Sep 24, 2013·Nature Nanotechnology·Stefan TenzerRoland H Stauber
Sep 26, 2013·Advanced Drug Delivery Reviews·Yu ChengMaciej S Lesniak
Oct 9, 2013·Proceedings of the National Academy of Sciences of the United States of America·Rachit AgarwalKrishnendu Roy
Oct 22, 2013·Drug Discovery Today·Abhalaxmi Singh, Sanjeeb K Sahoo
Nov 20, 2013·Journal of Nanoscience and Nanotechnology·Ningning MaNongyue Hel
Feb 5, 2014·Journal of Nanobiotechnology·Li ShangGerd Ulrich Nienhaus
Apr 16, 2014·Journal of Nanoscience and Nanotechnology·Massimo BottiniNunzio Bottini

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Citations

May 16, 2019·Chemical Society Reviews·Wei TangXiaoyuan Chen
Oct 17, 2017·Advanced Healthcare Materials·Vimala N BharadwajSarah E Stabenfeldt
Jan 9, 2021·Journal of Controlled Release : Official Journal of the Controlled Release Society·Rukhmani NarayanamurthyLarry D Unsworth

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