Glioblastoma-Derived Exosomes as Nanopharmaceutics for Improved Glioma Treatment

Authors:
Lee H, Bae K, Baek AR, Kwon EB, Kim YH, Nam SW, Lee GH, Chang Y
In:
Source: Pharmaceutics
Publication Date: (2022)
Issue: 14(5): 1002
Research Area:
Cancer Research/Cell Biology
Immunotherapy / Hematology
Stem Cells
Basic Research
Molecular Biology
Regenerative medicine
Drug Discovery
Cells used in publication:
U87
Species: human
Tissue Origin: brain
A549
Species: human
Tissue Origin: lung
Platform:
4D-Nucleofector® X-Unit
Experiment

2.3. Fabrication and Purification of Selu-Exo
Selumetinib (ChemScene, Monmouth Junction, NJ, USA, Cat. no. CS-0059, Lot. 78580)-loaded U87 MG-derived exosomes (U87-Selu exo) were fabricated by the electroporation method (4D Nucleofector; Lonza, Basel, Switzerland) using an Amaxa SE Cell Line 4D-NucleofectorTM X Kit L (24RCT, Catalog No. V4XC-1024; Lonza) according to the manufacturer’s instructions. The pulsation program for encapsulation was DS-126. The excess free selumetinib was removed by filtering through an Amicon Ultra 0.5 mL Centrifugal Filter (3K, Catalog No. UFC500396; Millipore) and washed twice with phosphate buffered saline (PBS) at pH 7.4 (1X, Catalog No. 10010 023, Gibco). For selumetinib loading into A549-derived exosomes (A549-Selu exo), Amaxa SF Cell Line 4D-NucleofectorTM X Kits L (24RCT, Catalog No. V4XC-2024; Lonza) and the CM-130 pulsation program were used. 

Abstract

The use of cancer-derived exosomes has been studied in several cancer types, but the cancer-targeting efficacy of glioma-derived exosomes has not been investigated in depth for malignant glioblastoma (GBM) cells. In this study, exosomes were derived from U87MG human glioblastoma cells, and selumetinib, a new anticancer drug, was loaded into the exosomes. We observed the tropism of GBM-derived exosomes in vitro and in vivo. We found that the tropism of GBM-derived exosomes is in contrast to the behavior of non-exosome-enveloped drugs and non-GBM-specific exosomes in vitro and in vivo in an animal GBM model. We found that the tropism exhibited by GBM-derived exosomes can be utilized to shuttle selumetinib, with no specific targeting moiety, to GBM tumor sites. Therefore, our findings indicated that GBM-derived exosomes loaded with selumetinib had a specific antitumor effect on U87MG cells and were non-toxic to normal brain cells. These exosomes offer improved therapeutic prospects for glioblastoma therapy.