Facilitated intracellular delivery of peptide-guided nanoparticles in tumor tissues

Jong Ho Kim, Sang Mun Bae, Moon Hee Na, Hyeri Shin, Yu Jin Yang, Kyung Hyun Min, Ki Young Choi, Kwangmeyung Kim, Rang Woon Park, Ick Chan Kwon, Byung Heon Lee, Allan S. Hoffman, In San Kim

Research output: Contribution to journalArticlepeer-review

41 Scopus citations

Abstract

Macromolecular nanoparticles can extravasate and accumulate within tumor tissues via the passive targeting system, reflecting enhanced permeability and the retention effect. However, the unsatisfactory tumor therapeutic efficacy of the passive-targeting system, attributable to the retention of extravasated nanoparticles in the vicinity of tumor vessels, argues that a new system that facilitates intracellular delivery of nanoparticles within tumors is needed. Here, we developed hydrophobically modified glycol chitosan (HGC) nanoparticles conjugated with interleukin-4 receptor (IL-4R) binding peptides, termed I4R, and tested them in mice bearing IL-4R-positive tumors. These HGC-I4R nanoparticles exhibited enhanced IL-4R-dependent cellular uptake in tumors compared to nonconjugated nanoparticles, leading to better therapeutic and imaging efficacy. We conclude that I4R facilitates and enhances cellular uptake of nanoparticles in tumor tissues. This study suggests that the intracelluar uptake of nanoparticles in tumors is an essential factor to consider in designing nanoparticles for tumor-targeted drug delivery and imaging.

Original languageEnglish
Pages (from-to)493-499
Number of pages7
JournalJournal of Controlled Release
Volume157
Issue number3
DOIs
StatePublished - 10 Feb 2012

Bibliographical note

Funding Information:
This research was supported by the WCU (World Class University) program through the Korea Science and Engineering Foundation ( R33-2008-000-10054-0 ), the National Research foundation of Korea (NRF) grant funded by the Korea government (MEST) ( 2010-0029206 , 2011-001043 0), and the Converging Research Center Program through the Ministry of Education, Science and Technology ( 2010K001054 ).

Keywords

  • Cancer imaging
  • Cancer therapy
  • Homing peptide
  • Nanoparticles
  • Tumor targeting

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