Effects of tumor microenvironments on targeted delivery of glycol chitosan nanoparticles
- Effects of tumor microenvironments on targeted delivery of glycol chitosan nanoparticles
- 권익찬; 김광명; 장혜윤; 윤홍열; 전상민; 심만규; 이지영; 고혜원; 민지웅; 나진희; 한현구; 김종호; 서민아; 이혁진; 박재형
- Enhanced permeability and retention effects; Glycol chitosan; Nanoparticle; Tumor microenvironment; Tumor-targeted delivery
- Issue Date
- Journal of controlled release
- VOL 267, NO S1-231
- 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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