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, Kwang Meyung Kim, Ick Chan Kwon

Research output: Contribution to journalArticle

18 Citations (Scopus)

Abstract

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
JournalJournal of Controlled Release
DOIs
Publication statusAccepted/In press - 2017

Fingerprint

Tumor Microenvironment
Nanoparticles
Permeability
Neoplasms
Chitosan
Nude Mice
Extracellular Matrix
glycol-chitosan
Nanomedicine
Blood Vessels

Keywords

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

ASJC Scopus subject areas

  • Pharmaceutical Science

Cite this

Effects of tumor microenvironments on targeted delivery of glycol chitosan nanoparticles. / Yhee, Ji Young; Jeon, Sangmin; Yoon, Hong Yeol; Shim, Man Kyu; Ko, Hyewon; Min, Jiwoong; Na, Jin Hee; Chang, Hyeyoun; Han, Hyounkoo; Kim, Jong Ho; Suh, Minah; Lee, Hyukjin; Park, Jae Hyung; Kim, Kwang Meyung; Kwon, Ick Chan.

In: Journal of Controlled Release, 2017.

Research output: Contribution to journalArticle

Yhee, JY, Jeon, S, Yoon, HY, Shim, MK, Ko, H, Min, J, Na, JH, Chang, H, Han, H, Kim, JH, Suh, M, Lee, H, Park, JH, Kim, KM & Kwon, IC 2017, 'Effects of tumor microenvironments on targeted delivery of glycol chitosan nanoparticles', Journal of Controlled Release. https://doi.org/10.1016/j.jconrel.2017.09.015
Yhee, Ji Young ; Jeon, Sangmin ; Yoon, Hong Yeol ; Shim, Man Kyu ; Ko, Hyewon ; Min, Jiwoong ; Na, Jin Hee ; Chang, Hyeyoun ; Han, Hyounkoo ; Kim, Jong Ho ; Suh, Minah ; Lee, Hyukjin ; Park, Jae Hyung ; Kim, Kwang Meyung ; Kwon, Ick Chan. / Effects of tumor microenvironments on targeted delivery of glycol chitosan nanoparticles. In: Journal of Controlled Release. 2017.
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AU - Yhee, Ji Young

AU - Jeon, Sangmin

AU - Yoon, Hong Yeol

AU - Shim, Man Kyu

AU - Ko, Hyewon

AU - Min, Jiwoong

AU - Na, Jin Hee

AU - Chang, Hyeyoun

AU - Han, Hyounkoo

AU - Kim, Jong Ho

AU - Suh, Minah

AU - Lee, Hyukjin

AU - Park, Jae Hyung

AU - Kim, Kwang Meyung

AU - Kwon, Ick Chan

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AB - 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.

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