A doxorubicin delivery platform using engineered natural membrane vesicle exosomes for targeted tumor therapy

Yanhua Tian, Suping Li, Jian Song, Tianjiao Ji, Motao Zhu, Gregory J. Anderson, Jingyan Wei, Guangjun Nie

Research output: Contribution to journalArticle

709 Scopus citations

Abstract

Targeted drug delivery vehicles with low immunogenicity and toxicity are needed for cancer therapy. Here we show that exosomes, endogenous nano-sized membrane vesicles secreted by most cell types, can deliver chemotherapeutics such as doxorubicin (Dox) to tumor tissue in BALB/c nude mice. To reduce immunogenicity and toxicity, mouse immature dendritic cells (imDCs) were used for exosome production. Tumor targeting was facilitated by engineering the imDCs to express a well-characterized exosomal membrane protein (Lamp2b) fused to αv integrin-specific iRGD peptide (CRGDKGPDC). Purified exosomes from imDCs were loaded with Dox via electroporation, with an encapsulation efficiency of up to 20%. iRGD exosomes showed highly efficient targeting and Dox delivery to αv integrin-positive breast cancer cells invitro as demonstrated by confocal imaging and flow cytometry. Intravenously injected targeted exosomes delivered Dox specifically to tumor tissues, leading to inhibition of tumor growth without overt toxicity. Our results suggest that exosomes modified by targeting ligands can be used therapeutically for the delivery of Dox to tumors, thus having great potential value for clinical applications.

Original languageEnglish (US)
Pages (from-to)2383-2390
Number of pages8
JournalBiomaterials
Volume35
Issue number7
DOIs
StatePublished - Feb 2014

Keywords

  • αv Integrin-positive cancer cells
  • Doxorubicin
  • Exosome
  • IRGD
  • Tumor therapy

ASJC Scopus subject areas

  • Biomaterials
  • Bioengineering
  • Ceramics and Composites
  • Mechanics of Materials
  • Biophysics

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