Glutathione-responsive nano-vehicles as a promising platform for targeted intracellular drug and gene delivery

Ru Cheng, Fang Feng, Fenghua Meng, Chao Deng, Jan Feijen, Zhiyuan Zhong

Research output: Contribution to journalArticleAcademicpeer-review

838 Citations (Scopus)

Abstract

The past couple of years have witnessed a tremendous progress in the development of glutathione-responsive nano-vehicles for targeted intracellular drug and gene delivery, as driven by the facts that (i) many therapeutics (e.g. anti-cancer drugs, photosensitizers, and anti-oxidants) and biotherapeutics (e.g. peptide and protein drugs, and siRNA) exert therapeutical effects only inside cells like the cytosol and cell nucleus, and (ii) several intracellular compartments such as cytosol, mitochondria, and cell nucleus contain a high concentration of glutathione (GSH) tripeptides (about 2–10 mM), which is 100 to 1000 times higher than that in the extracellular fluids and circulation (about 2–20 μM). Glutathione has been recognized as an ideal and ubiquitous internal stimulus for rapid destabilization of nano-carriers inside cells to accomplish efficient intracellular drug release. In this paper, we will review recent results on GSH-responsive nano-vehicles in particular micelles, nanoparticles, capsules, polymersomes, nanogels, dendritic and macromolecular drug conjugates, and nano-sized nucleic acid complexes for controlled delivery of anti-cancer drugs (e.g. doxorubicin and paclitaxel), photosensitizers, anti-oxidants, peptides, protein drugs, and nucleic acids (e.g. DNA, siRNA, and antisense oligodeoxynucleotide). The unique disulfide chemistry has enabled novel and versatile designs of multifunctional delivery systems addressing both intracellular and extracellular barriers. We are convinced that GSH-responsive nano-carrier systems have enormous potential in targeted cancer therapy.
Original languageEnglish
Pages (from-to)2-12
JournalJournal of controlled release
Volume152
Issue number1
DOIs
Publication statusPublished - 2011

Keywords

  • METIS-284175
  • IR-89551

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