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Author Notes:

Correspondence to: Shuming Nie, snie@emory.edu.

Disclosure: One of the authors (S.N.) is a scientific consultant of Spectropath Inc., a company to further develop and commercialize devices and contrast agents for image- guided cancer surgery.

Publisher's Disclaimer: This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final citable form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain.


Research Funding:

We acknowledge the National Institutes of Health for financial support (grants R01CA163256, RC2CA148265, and HHSN268201000043C to S.N.). Go to:


  • Hypoxia
  • Matrix metalloproteinases
  • Nanomedicine
  • Tumor heterogeneity
  • Tumor microenvironment
  • pH
  • Animals
  • Enzyme Activation
  • Humans
  • Hydrogen-Ion Concentration
  • Hypoxia
  • Nanoparticles
  • Neoplasms
  • Tumor Microenvironment

Stimuli-responsive nanoparticles for targeting the tumor microenvironment


Journal Title:

Journal of Controlled Release


Volume 219


, Pages 205-214

Type of Work:

Article | Post-print: After Peer Review


One of the most challenging and clinically important goals in nanomedicine is to deliver imaging and therapeutic agents to solid tumors. Here we discuss the recent design and development of stimuli-responsive smart nanoparticles for targeting the common attributes of solid tumors such as their acidic and hypoxic microenvironments. This class of stimuli-responsive nanoparticles is inactive during blood circulation and under normal physiological conditions, but is activated by acidic pH, enzymatic up-regulation, or hypoxia once they extravasate into the tumor microenvironment. The nanoparticles are often designed to first "navigate" the body's vascular system, "dock" at the tumor sites, and then "activate" for action inside the tumor interstitial space. They combine the favorable biodistribution and pharmacokinetic properties of nanodelivery vehicles and the rapid diffusion and penetration properties of smaller drug cargos. By targeting the broad tumor habitats rather than tumor-specific receptors, this strategy has the potential to overcome the tumor heterogeneity problem and could be used to design diagnostic and therapeutic nanoparticles for a broad range of solid tumors.

Copyright information:

© 2015 Elsevier B.V.

This is an Open Access work distributed under the terms of the Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License (http://creativecommons.org/licenses/by-nc-nd/4.0/).

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