MSC-derived exosomes enhance the anticancer activity of drugs in 3D spheroid of breast cancer cells

Abstract

The unique properties of the MSC-derived exosome (MSC-Exos) make it an interesting drug-delivery tool for tumor cells. Drug delivery via exosomes helps overcome challenges to access the core of solid tumors. Here, we investigated exosomal chemotherapy drug formulations on the 3D multicellular spheroid models of breast cancer cell lines. The multicellular 3D spheroid of BT-474 and MDA-MB-231 breast cancer cell lines were made by liquid overlay technique. MSC-Exos were isolated from adipose-derived mesenchymal stem cells (ADMSCs) culture medium and characterized by their biological characteristics. Then paclitaxel (PTX) and cisplatin (CIS) were loaded into MSC-Exos. The cellular uptake and cytotoxic effect of these nanocarriers were evaluated by MTT and flow cytometry. MSC-Exos could efficiently facilitate cellular uptake in multicellular spheroids of breast cancer cell lines. EXO-PTX significantly inhibited the growth of spheroid in both MDA-MB-231 and BT-474 multicellular spheroids (P < 0.001). Moreover, apoptosis was more prominently inducted by EXO-PTX compared to the free PTX (P < 0.03). For cisplatin, although the exosomal formulation contained lower drug concentration compared to the free drug, the potency was increased. Based on our findings, the exosomal formulation of drugs induced higher toxicity and apoptosis in the 3D multicellular spheroids model with considerably lower drug concentrations. Drug-loaded MSC-Exos could be a potentially suitable alternative for cancer chemotherapy practices.