Effects of tumor microenvironments on targeted delivery of glycol chitosan nanoparticles

Ji Young Yhee, Sangmin Jeon, Hong Yeol Yoon, Man Kyu Shim, Hyewon Ko, Jiwoong Min, Jin Hee Na, Hyeyoun Chang, Hyounkoo Han, Jong Ho Kim, Minah Suh, Hyukjin Lee, Jae Hyung Park, Kwangmeyung Kim, Ick Chan Kwon

Research output: Contribution to journalArticlepeer-review

61 Scopus citations


In cancer theranostics, the main strategy of nanoparticle-based targeted delivery system has been understood by enhanced permeability and retention (EPR) effect of macromolecules. Studies on diverse nanoparticles provide a better understanding of different EPR effects depending on their structure, physicochemical properties, and chemical modifications. Recently the tumor microenvironment has been considered as another important factor for determining tumor-targeted delivery of nanoparticles, but the correlation between EPR effects and tumor microenvironment has not yet been fully elucidated. Herein, ectopic subcutaneous tumor models presenting different tumor microenvironments were established by inoculation of SCC7, U87, HT29, PC3, and A549 cancer cell lines into athymic nude mice, respectively. In the five different types of tumor-bearing mice, tumor-targeted delivery of self-assembled glycol chitosan nanoparticles (CNPs) were comparatively evaluated to identify the correlation between the tumor microenvironments and targeted delivery of CNPs. As a result, neovascularization and extents of intratumoral extracellular matrix (ECM) were both important in determining the tumor targeted delivery of CNPs. The EPR effect was maximized in the tumors which include large extent of angiogenic blood vessels and low intratumoral ECM content. This comprehensive study provides substantial evidence that the EPR effects based tumor-targeted delivery of nanoparticles can be different depending on the tumor microenvironment in individual tumors. To overcome current limitations in clinical nanomedicine, the tumor microenvironment of the patients and EPR effects in clinical tumors should also be carefully studied.

Original languageEnglish
Pages (from-to)223-231
Number of pages9
JournalJournal of Controlled Release
StatePublished - 10 Dec 2017

Bibliographical note

Funding Information:
This work was supported by the GiRC ( NRF-2012K1A1A2A01055811 ), the GRL project ( NRF-2013K1A1A2A02050115 ), the KU-KIST project and the Intramural Research Program of KIST.

Publisher Copyright:
© 2017 Elsevier B.V.


  • Enhanced permeability and retention effects
  • Glycol chitosan
  • Nanoparticle
  • Tumor microenvironment
  • Tumor-targeted delivery


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