Stimuli-responsive nanoparticles for targeting the tumor microenvironment

• Type of Material: Article
• Authors: Jinzhi Du, Emory University; Lucas A. Lane, Emory University; Shuming Nie, Emory University
• Language: English
• Date: 2015-12-10
• Publisher: Elsevier
• Publication Version: Author Accepted Manuscript (After Peer Review)
• Copyright Statement: © 2015 Elsevier B.V.
• License: Creative Commons Attribution-NonCommercial-NoDerivs 4.0 International
• Final Published Version (URL): http://dx.doi.org/10.1016/j.jconrel.2015.08.050
• Title of Journal or Parent Work: Journal of Controlled Release
• ISSN: 0168-3659
• Volume: 219
• Start Page: 205
• End Page: 214
• Grant/Funding Information: We acknowledge the National Institutes of Health for financial support (grants R01CA163256, RC2CA148265, and HHSN268201000043C to S.N.). Go to:
• Keywords: Humans; Animals; Nanomedicine; Enzyme Activation; Nanoparticles; Hypoxia; Tumor heterogeneity; Tumor microenvironment; Matrix metalloproteinases; Tumor Microenvironment; Hydrogen-Ion Concentration; Neoplasms; pH
• Research Categories: Health Sciences, Oncology; Engineering, Biomedical

Abstract

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.