Subin Kang, Mincheol Son, Minji Kang, Jae Young Park, Kangmin Park, Minhyung Lee
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引用次数: 0
Abstract
Glioblastoma is a devastating disease with a high mortality rate. Gene therapy with anti-microRNA inhibitors has been suggested as a new modality for treatment of glioblastoma. In this study, glioblastoma-targeted extracellular vesicles (EVs) were produced with specific ligands and evaluated as a carrier of anti-microRNA-21 oligonucleotides (AMO21). Angiopep-2 (ANG) and chlorotoxin (CTX) were linked to EVs by DNA recombination techniques. Cholesterol-conjugated AMO21 (AMO21c) was loaded onto the EVs decorated with ANG or CTX (ANG-EV or CTX-EV) by hydrophobic interactions. In vitro cellular uptake assays indicated that CTX-EV had higher delivery efficiency than unmodified EV (Unmod-EV) and ANG-EV. In addition, CTX-EV had higher transcytosis efficiency than the other EVs, suggesting that it effectively passes through the blood-brain barrier. In orthotopic glioblastoma animal models, CTX-EV delivered AMO21c more efficiently than Lipofectamine/AMO21c, Unmod-EV/AMO21c and ANG-EV/AMO21c. As a result, a greater decrease in tumour size with CTX-EV/AMO21c was observed, as compared with Lipofectamine/AMO21c, Unmod-EV/AMO21c and ANG-EV/AMO21c. CTX-EV/AMO21c induced the expression of the phosphatase and tensin homolog (PTEN) and programmed cell death 4 (PDCD4) genes in tumours. In addition, apoptosis levels in tumour tissues were enhanced by CTX-EV/AMO21c, as compared with the other samples. In conclusion, CTX-EV is effective for targeted delivery of AMO21 to glioblastoma and may have potential in glioblastoma gene therapy.
期刊介绍：
Journal of Drug Targeting publishes papers and reviews on all aspects of drug delivery and targeting for molecular and macromolecular drugs including the design and characterization of carrier systems (whether colloidal, protein or polymeric) for both vitro and/or in vivo applications of these drugs.
Papers are not restricted to drugs delivered by way of a carrier, but also include studies on molecular and macromolecular drugs that are designed to target specific cellular or extra-cellular molecules. As such the journal publishes results on the activity, delivery and targeting of therapeutic peptides/proteins and nucleic acids including genes/plasmid DNA, gene silencing nucleic acids (e.g. small interfering (si)RNA, antisense oligonucleotides, ribozymes, DNAzymes), as well as aptamers, mononucleotides and monoclonal antibodies and their conjugates. The diagnostic application of targeting technologies as well as targeted delivery of diagnostic and imaging agents also fall within the scope of the journal. In addition, papers are sought on self-regulating systems, systems responsive to their environment and to external stimuli and those that can produce programmed, pulsed and otherwise complex delivery patterns.
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