Targeted intracellular delivery of proteins with spatial and temporal control

Demosthenes P. Morales, Gary B. Braun, Alessia Pallaoro, Renwei Chen, Xiao Huang, Joseph A. Zasadzinski, Norbert O. Reich

Research output: Contribution to journalArticlepeer-review

25 Scopus citations


While a host of methods exist to deliver genetic materials or small molecules to cells, very few are available for protein delivery to the cytosol. We describe a modular, light-activated nanocarrier that transports proteins into cells by receptor-mediated endocytosis and delivers the cargo to the cytosol by light triggered endosomal escape. The platform is based on hollow gold nanoshells (HGN) with polyhistidine tagged proteins attached through an avidity-enhanced, nickel chelation linking layer; here, we used green fluorescent protein (GFP) as a model deliverable cargo. Endosomal uptake of the GFP loaded nanocarrier was mediated by a C-end Rule (CendR) internalizing peptide fused to the GFP. Focused femtosecond pulsed-laser excitation triggered protein release from the nanocarrier and endosome disruption, and the released protein was capable of targeting the nucleoli, a model intracellular organelle. We further demonstrate the generality of the approach by loading and releasing Sox2 and p53. This method for targeting of individual cells, with resolution similar to microinjection, provides spatial and temporal control over protein delivery.

Original languageEnglish (US)
Pages (from-to)600-609
Number of pages10
JournalMolecular pharmaceutics
Issue number2
StatePublished - Feb 2 2015

Bibliographical note

Publisher Copyright:
© 2014 American Chemical Society.

Copyright 2016 Elsevier B.V., All rights reserved.


  • endosome escape
  • gold
  • nanoshell
  • near-infrared laser
  • protein delivery
  • targeted delivery

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