A networked swellable dextrin nanogels loading Bcl2 siRNA for melanoma tumor therapy

Huipeng Li, Zhanwei Zhou, Feiran Zhang, Yuxin Guo, Xue Yang, Hulin Jiang, Fei Tan, David Oupicky, Minjie Sun

Research output: Contribution to journalArticle

4 Scopus citations

Abstract

In this study, a networked swellable dextrin nanogel (DNG) was developed to achieve stimulated responsive small interfering RNA (siRNA) release for melanoma tumor therapy. siRNA was loaded into multidimensional dextrin nanogels by charge condensation with positive arginine residues modified in the dextrin backbone. Moreover, the networked nanogel was destroyed and loosened based on its bioreducible responsive property to control accelerated siRNA release in a bioreducible intracellular environment, while it remained stable under normal physiological conditions. We demonstrated that DNGs had swellable and disassembly properties under reduced buffer condition by transmission electron microscopy evaluation. The DNGs achieved an endosomal escape followed by selective release of the cargo into the cytosol by glutathione-triggered disassembly according to confocal microscopy observation. Thus, this smart nanogel achieved outstanding luciferase gene silencing efficiency and decreased Bcl2 protein expression in vitro and in vivo based on western blot analysis. Moreover, this nanogel exhibited superior anti-tumor activity for B16F10 xenograft tumors in C57BL/6 mice. These results demonstrate that the networked DNGs are effective for gene condensation and controlled intracellular release for tumor therapy. Overall, these findings suggest that this multidimensional swellable stimuli-responsive dextrin nanogel is an innovative strategy with great promise for gene and drug delivery. [Figure not available: see fulltext.].

Original languageEnglish (US)
Pages (from-to)4627-4642
Number of pages16
JournalNano Research
Volume11
Issue number9
DOIs
StatePublished - Sep 1 2018

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Keywords

  • dextrin nanogels
  • disulfide cross-linked
  • local enrichment
  • lysosomal escape
  • reduction-responsive
  • small interfering RNA (siRNA) delivery

ASJC Scopus subject areas

  • Materials Science(all)
  • Electrical and Electronic Engineering

Cite this

Li, H., Zhou, Z., Zhang, F., Guo, Y., Yang, X., Jiang, H., Tan, F., Oupicky, D., & Sun, M. (2018). A networked swellable dextrin nanogels loading Bcl2 siRNA for melanoma tumor therapy. Nano Research, 11(9), 4627-4642. https://doi.org/10.1007/s12274-018-2044-6