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Exploring the Tumor Microenvironment with Nanoparticles

  • Lei Miao
  • Leaf HuangEmail author
Chapter
Part of the Cancer Treatment and Research book series (CTAR, volume 166)

Abstract

Recent developments in nanotechnology have brought new approaches to cancer diagnosis and therapy. While enhanced permeability and retention effect (EPR) promotes nanoparticle (NP) extravasation, the abnormal tumor vasculature, high interstitial pressure and dense stroma structure limit homogeneous intratumoral distribution of NP and compromise their imaging and therapeutic effect. Moreover, heterogeneous distribution of NP in nontumor-stroma cells damages the nontumor cells, and interferes with tumor-stroma crosstalk. This can lead to inhibition of tumor progression, but can also paradoxically induce acquired resistance and facilitate tumor cell proliferation and metastasis. Overall, the tumor microenvironment plays a crucial, yet controversial role in regulating NP distribution and their biological effects. In this review, we summarize recent studies on the stroma barriers for NP extravasation, and discuss the consequential effects of NP distribution in stroma cells. We also highlight design considerations to improve NP delivery and propose potential combinatory strategies to overcome acquired resistance induced by damaged stroma cells.

Keywords

Nanoparticle Tumor microenvironment Extracellular matrix Pericytes tumor-associated fibroblast 

Acronyms

EPR

Enhanced Permeability and Retention Effect

ECM

Extracellular Matrix

TME

Tumor Microenvironment

BM

Basement Membrane

IFP

Interstitial Fluidic Pressure

TAF

Tumor Associated Fibroblast

TAM

Tumor Associated Macrophage

MMP

Matrix Metalloproteinases

NP

Nanoparticles

Notes

Acknowledgments

This work was supported by NIH grant support: CA149363, CA151652, CA149387 and DK100664. The authors thank Andrew Mackenzie Blair for his assistance in the chapter preparation.

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Copyright information

© Springer International Publishing Switzerland 2015

Authors and Affiliations

  1. 1.Division of Molecular Pharmaceutics and Center of Nanotechnology in Drug Delivery, Eshelman School of PharmacyUniversity of North Carolina at Chapel HillChapel HillUSA

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