Details

Autor(en) / Beteiligte

• Kalimuthu, Senthilkumar
• Gangadaran, Prakash
• Rajendran, Ramya Lakshmi
• Zhu, Liya
• Oh, Ji Min
• Lee, Ho Won
• Gopal, Arunnehru
• Baek, Se Hwan
• Jeong, Shin Young
• Lee, Sang-Woo
• Lee, Jaetae
• Ahn, Byeong-Cheol

Titel

A New Approach for Loading Anticancer Drugs Into Mesenchymal Stem Cell-Derived Exosome Mimetics for Cancer Therapy

Ist Teil von

• Frontiers in pharmacology, 2018-09, Vol.9, p.1116-1116

Ort / Verlag

Switzerland: Frontiers Media S.A

Erscheinungsjahr

2018

Quelle

EZB Electronic Journals Library

Beschreibungen/Notizen

• Exosomes derived from mesenchymal stem cells (MSCs) have been evaluated for their potential to be used as drug delivery vehicles. Synthetically personalized exosome mimetics (EMs) could be the alternative vesicles for drug delivery. In this study, we aimed to isolate EMs from human MSCs. Cells were mixed with paclitaxel (PTX) and PTX-loaded EMs (PTX-MSC-EMs) were isolated and evaluated for their anticancer effects against breast cancer. EMs were isolated from human bone marrow-derived MSCs. MSCs (4 × 10 cells/mL) were mixed with or without PTX at different concentrations in phosphate-buffered saline (PBS) and serially extruded through 10-, 5-, and 1-μm polycarbonate membrane filters using a mini-extruder. MSCs were centrifuged to remove debris and the supernatant was filtered through a 0.22-μm filter, followed by ultracentrifugation to isolate EMs and drug-loaded EMs. EMs without encapsulated drug (MSC-EMs) and those with encapsulated PTX (PTX-MSC-EMs) were characterized by western blotting, nanoparticle tracking analysis (NTA), and transmission electron microscopy (TEM). The anticancer effects of MSC-EMs and PTX-MSC-EMs were assessed with breast cancer (MDA-MB-231) cells both and using optical imaging. EMs were isolated by the extrusion method and ultracentrifugation. The isolated vesicles were positive for membrane markers (ALIX and CD63) and negative for golgi (GM130) and endoplasmic (calnexin) marker proteins. NTA revealed the size of MSC-EM to be around 149 nm, while TEM confirmed its morphology. PTX-MSC-EMs significantly ( < 0.05) decreased the viability of MDA-MB-231 cells at increasing concentrations of EM. The tumor growth was significantly inhibited by PTX-MSC-EMs as compared to control and/or MSC-EMs. Thus, MSC-EMs were successfully isolated using simple procedures and drug-loaded MSC-EMs were shown to be therapeutically efficient for the treatment of breast cancer both and . MSC-EMs may be used as drug delivery vehicles for breast cancers.