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

Biomaterials

Animals, Antibiotics, Antineoplastic, administration & dosage, therapeutic use, Base Sequence, Cell Line, Tumor, Doxorubicin, Drug Delivery Systems, Electrophoresis, Agar Gel, Humans, Mice, Mice, Inbred BALB C, Mice, Nude, Microscopy, Electron, Neoplasms, drug therapy, Oligodeoxyribonucleotides

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      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 in vitro 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. Copyright © 2013 Elsevier Ltd. All rights reserved.

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      Journal
      24345736
      10.1016/j.biomaterials.2013.11.083

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