In vivo tumor targeting and radionuclide imaging with self-assembled nanoparticles: Mechanisms, key factors, and their implications

Yong Woo Cho, Soo Ah Park, Tae Hee Han, Dai Hyun Son, Ji Sun Park, Seung Jun Oh, Dae Hyuk Moon, Kyung Ja Cho, Cheol Hee Ahn, Youngro Byun, In-San Kim, Ick Chan Kwon, Sang Yoon Kim

Research output: Contribution to journalArticle

105 Citations (Scopus)

Abstract

The development of more selective delivery systems for cancer diagnosis and chemotherapy is one of the most important goals of current anticancer research. The purpose of this study is to evaluate various self-assembled nanoparticles as candidates to shuttle radionuclide and/or drugs into tumors and to investigate the mechanisms underlying the tumor targeting with self-assembled nanoparticles. By combining different hydrophobic moieties and hydrophilic polymer backbones, various self-assembled nanoparticles were prepared, and their in vivo distributions in tumor-bearing mice were studied by radionuclide imaging. One type of nanoparticles (fluorescein isothiocyanate-conjugated glycol chitosan (FGC) nanoparticles) exhibited highly selective tumoral localization. Scintigraphic images obtained 1 day after the intravenous injection of FGC nanoparticles clearly delineated the tumor against adjacent tissues. The mechanisms underlying the tumor targeting with self-assembled nanoparticles were investigated in terms of the physicochemical properties of nanoparticles and tumor microenvironments. FGC nanoparticles were preferentially localized in perivascular regions, implying their extravasation to tumors through the hyperpermeable tumor vasculature. The magnitude and pattern of tumoral distribution of self-assembled nanoparticles were influenced by several key factors -(i) in vivo colloidal stability: nanoparticles should maintain their intact nanostructures in vivo for a long period of time, (ii) particle size, (iii) intracellular uptake of nanoparticle: fast cellular uptake greatly facilitates the tumor targeting, (iv) tumor angiogenesis: pathological angiogenesis permits access of nanoparticles to tumors. We believe that this work can provide insight for the engineering of nanoparticles and be extended to cancer therapy and diagnosis, so as to deliver multiple therapeutic agents and imaging probes at high local concentrations.

Original languageEnglish
Pages (from-to)1236-1247
Number of pages12
JournalBiomaterials
Volume28
Issue number6
DOIs
Publication statusPublished - 2007 Feb 1
Externally publishedYes

Keywords

  • Angiogenesis
  • Drug delivery
  • Radionuclide imaging
  • Self-assembled nanoparticles
  • Tumor targeting

ASJC Scopus subject areas

  • Biotechnology
  • Bioengineering
  • Biomedical Engineering

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  • Cite this

    Cho, Y. W., Park, S. A., Han, T. H., Son, D. H., Park, J. S., Oh, S. J., Moon, D. H., Cho, K. J., Ahn, C. H., Byun, Y., Kim, I-S., Kwon, I. C., & Kim, S. Y. (2007). In vivo tumor targeting and radionuclide imaging with self-assembled nanoparticles: Mechanisms, key factors, and their implications. Biomaterials, 28(6), 1236-1247. https://doi.org/10.1016/j.biomaterials.2006.10.002