Minimalism in fabrication of self-organized nanogels holding both anti-cancer drug and targeting moiety

Sungwon Kim, Kyong Mi Park, Jin Young Ko, Ick Chan Kwon, Hyeon Geun Cho, Dongmin Kang, In Tag Yu, Kwangmeyung Kim, Kun Na

Research output: Contribution to journalArticle

37 Citations (Scopus)

Abstract

Recent researches to develop nano-carrier systems in anti-cancer drug delivery have focused on more complicated design to improve therapeutic efficacy and to reduce side effects. Although such efforts have great impact to biomedical science and engineering, the complexity has been a huddle because of clinical and economic problems. In order to overcome the problems, a simplest strategy to fabricate nano-carriers to deliver doxorubicin (DOX) was proposed in the present study. Two significant subjects (i) formation of nanoparticles loading and releasing DOX and (ii) binding specificity of them to cells, were examined. Folic acid (FA) was directly coupled with pullulan (Pul) backbone by ester linkage (FA/Pul conjugate) and the degree of substitution (DS) was varied, which were confirmed by 1H NMR and UV spectrophotometry. Light scattering results revealed that the nanogels possessed two major size distributions around 70 and 270 nm in an aqueous solution. Their critical aggregation concentrations (CACs) were less than 10 μg/mL, which are lower than general critical micelle concentrations (CMCs) of low-molecular-weight surfactants. Transmission electron microscopy (TEM) images showed well-dispersed nanogel morphology in a dried state. Depending on the DS, the nanogels showed different DOX-loading and releasing profiles. The DOX release rate from FA8/Pul (with the highest DS) for 24 h was slower than that from FA4/or FA6/Pul, indicating that the FA worked as a hydrophobic moiety for drug holding. Cellular uptake of the nanogels (KB cells) was also monitored by confocal microscopy. All nanogels were internalized regardless of the DS of FA. Based on the results, the objectives of this study, to suggest a new method overcoming the complications in the drug carrier design, were successfully verified.

Original languageEnglish
Pages (from-to)55-63
Number of pages9
JournalColloids and Surfaces B: Biointerfaces
Volume63
Issue number1
DOIs
Publication statusPublished - 2008 May 1

Keywords

  • Cancer
  • Doxorubicin
  • Folate
  • Nanogels
  • Pullulan
  • Self-organized

ASJC Scopus subject areas

  • Biotechnology
  • Surfaces and Interfaces
  • Physical and Theoretical Chemistry
  • Colloid and Surface Chemistry

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