Carrier-free nanoparticles of cathepsin B-cleavable peptide-conjugated doxorubicin prodrug for cancer targeting therapy

Man Kyu Shim, Jooho Park, Hong Yeol Yoon, Sangmin Lee, Wooram Um, Jong Ho Kim, Sun Woong Kang, Joung Wook Seo, Soo Wang Hyun, Jae Hyung Park, Youngro Byun, Ick Chan Kwon, Kwangmeyung Kim

Research output: Contribution to journalArticlepeer-review

89 Citations (Scopus)


Cancer nanomedicine using nanoparticle-based delivery systems has shown outstanding promise in recent decades for improving anticancer treatment. However, limited targeting efficiency, low drug loading efficiency and innate toxicity of nanoparticles have caused severe problems, leaving only a few available in the clinic. Here, we newly developed carrier-free nanoparticles of cathepsin B-cleavable peptide (Phe-Arg-Arg-Gly; FRRG)-conjugated doxorubicin (DOX) prodrug (FRRG-DOX) that formed a stable nanoparticle structure with an average diameter of 213 nm in aqueous condition. The carrier-free nanoparticles of FRRG-DOX induced cytotoxicity against cathepsin B-overexpressed tumor cells whereas the toxicity was minimized in normal cells. In particular, the FRRG-DOX nanoparticles showed the successful tumor-targeting ability and enhanced therapeutic efficiency in human colon adenocarcinoma (HT-29) tumor-bearing mice via enhanced permeation and retention (EPR) effect. Furthermore, FRRG-DOX nanoparticles did not present any severe toxicity, such as non-specific cell death and cardiac toxicity, in normal tissues due to minimal expression of cathepsin B. This carrier-free nanoparticles of FRRG-DOX can solve the unavoidable problems of current nanomedicine, such as lower targeting efficiency, toxicity of nanoparticles themselves, and difficulty in mass production that are fatally caused by natural and synthetic nano-sized carriers.

Original languageEnglish
Pages (from-to)376-389
Number of pages14
JournalJournal of Controlled Release
Publication statusPublished - 2019 Jan 28


  • Carrier-free nanoparticles
  • Cathepsin B-specfic prodrug
  • Nanomedicine
  • Tumor targeting therapy

ASJC Scopus subject areas

  • Pharmaceutical Science


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