Taxol-Loaded MSC-Derived Exosomes Provide a Therapeutic Vehicle to Target Metastatic Breast Cancer and Other Carcinoma Cells
MSC-derived exosomes display, among others, an efficient biocompatibility and a reduced intrinsic immunogenicity, representing a valuable vehicle for drug delivery in a tumor-therapeutic approach. Following treatment of several human mesenchymal stroma/stem-like cell (MSC) populations with sub-letha...
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doaj-1e3bc6e6fffa41f8abbd74c2120627712020-11-25T00:31:13ZengMDPI AGCancers2072-66942019-06-0111679810.3390/cancers11060798cancers11060798Taxol-Loaded MSC-Derived Exosomes Provide a Therapeutic Vehicle to Target Metastatic Breast Cancer and Other Carcinoma CellsCatharina Melzer0Vanessa Rehn1Yuanyuan Yang2Heike Bähre3Juliane von der Ohe4Ralf Hass5Biochemistry and Tumor Biology Lab, Department of Obstetrics and Gynecology, Hannover Medical School, 30625 Hannover, GermanyBiochemistry and Tumor Biology Lab, Department of Obstetrics and Gynecology, Hannover Medical School, 30625 Hannover, GermanyBiochemistry and Tumor Biology Lab, Department of Obstetrics and Gynecology, Hannover Medical School, 30625 Hannover, GermanyInstitute of Pharmacology, Hannover Medical School, 30625 Hannover, GermanyBiochemistry and Tumor Biology Lab, Department of Obstetrics and Gynecology, Hannover Medical School, 30625 Hannover, GermanyBiochemistry and Tumor Biology Lab, Department of Obstetrics and Gynecology, Hannover Medical School, 30625 Hannover, GermanyMSC-derived exosomes display, among others, an efficient biocompatibility and a reduced intrinsic immunogenicity, representing a valuable vehicle for drug delivery in a tumor-therapeutic approach. Following treatment of several human mesenchymal stroma/stem-like cell (MSC) populations with sub-lethal concentrations of taxol for 24 h, exosomes were isolated and applied to different human cancer populations including A549 lung cancer, SK-OV-3 ovarian cancer, and MDA-hyb1 breast cancer cells. While MSC control exosomes revealed little if any growth inhibition on the tumor cells, exposure to taxol-loaded MSC-derived exosomes was associated with 80−90% cytotoxicity. A similar application of taxol-loaded exosomes from HuVEC displayed much fewer effects. Quantification by LC-MS/MS analysis demonstrated a 7.6-fold reduced taxol concentration in MSC exosomes when compared to equivalent cytotoxic in vitro effects achieved with taxol substances, indicating a specific and more efficient tumor-targeting property. Consequently, MSC-derived taxol exosomes were tested in vivo. Highly metastatic MDA-hyb1 breast tumors were induced in NODscid mice, and systemic intravenous application of MSC-derived taxol exosomes revealed a more than 60% reduction of subcutaneous primary tumors. Moreover, the amount of distant organ metastases observed at least in lung, liver, spleen, and kidney was reduced by 50% with MSC taxol exosomes, similar to the effects observed with taxol, although the concentration of taxol in exosomes was about 1000-fold reduced. Together, these findings in different cancer cell populations and in vivo provide promising future perspectives for drug-loaded MSC-derived exosomes in efficiently targeting primary tumors and metastases by reducing side effects.https://www.mdpi.com/2072-6694/11/6/798therapeutic exosomesmesenchymal stem cellstargeted therapycancer cellstumor therapy |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Catharina Melzer Vanessa Rehn Yuanyuan Yang Heike Bähre Juliane von der Ohe Ralf Hass |
spellingShingle |
Catharina Melzer Vanessa Rehn Yuanyuan Yang Heike Bähre Juliane von der Ohe Ralf Hass Taxol-Loaded MSC-Derived Exosomes Provide a Therapeutic Vehicle to Target Metastatic Breast Cancer and Other Carcinoma Cells Cancers therapeutic exosomes mesenchymal stem cells targeted therapy cancer cells tumor therapy |
author_facet |
Catharina Melzer Vanessa Rehn Yuanyuan Yang Heike Bähre Juliane von der Ohe Ralf Hass |
author_sort |
Catharina Melzer |
title |
Taxol-Loaded MSC-Derived Exosomes Provide a Therapeutic Vehicle to Target Metastatic Breast Cancer and Other Carcinoma Cells |
title_short |
Taxol-Loaded MSC-Derived Exosomes Provide a Therapeutic Vehicle to Target Metastatic Breast Cancer and Other Carcinoma Cells |
title_full |
Taxol-Loaded MSC-Derived Exosomes Provide a Therapeutic Vehicle to Target Metastatic Breast Cancer and Other Carcinoma Cells |
title_fullStr |
Taxol-Loaded MSC-Derived Exosomes Provide a Therapeutic Vehicle to Target Metastatic Breast Cancer and Other Carcinoma Cells |
title_full_unstemmed |
Taxol-Loaded MSC-Derived Exosomes Provide a Therapeutic Vehicle to Target Metastatic Breast Cancer and Other Carcinoma Cells |
title_sort |
taxol-loaded msc-derived exosomes provide a therapeutic vehicle to target metastatic breast cancer and other carcinoma cells |
publisher |
MDPI AG |
series |
Cancers |
issn |
2072-6694 |
publishDate |
2019-06-01 |
description |
MSC-derived exosomes display, among others, an efficient biocompatibility and a reduced intrinsic immunogenicity, representing a valuable vehicle for drug delivery in a tumor-therapeutic approach. Following treatment of several human mesenchymal stroma/stem-like cell (MSC) populations with sub-lethal concentrations of taxol for 24 h, exosomes were isolated and applied to different human cancer populations including A549 lung cancer, SK-OV-3 ovarian cancer, and MDA-hyb1 breast cancer cells. While MSC control exosomes revealed little if any growth inhibition on the tumor cells, exposure to taxol-loaded MSC-derived exosomes was associated with 80−90% cytotoxicity. A similar application of taxol-loaded exosomes from HuVEC displayed much fewer effects. Quantification by LC-MS/MS analysis demonstrated a 7.6-fold reduced taxol concentration in MSC exosomes when compared to equivalent cytotoxic in vitro effects achieved with taxol substances, indicating a specific and more efficient tumor-targeting property. Consequently, MSC-derived taxol exosomes were tested in vivo. Highly metastatic MDA-hyb1 breast tumors were induced in NODscid mice, and systemic intravenous application of MSC-derived taxol exosomes revealed a more than 60% reduction of subcutaneous primary tumors. Moreover, the amount of distant organ metastases observed at least in lung, liver, spleen, and kidney was reduced by 50% with MSC taxol exosomes, similar to the effects observed with taxol, although the concentration of taxol in exosomes was about 1000-fold reduced. Together, these findings in different cancer cell populations and in vivo provide promising future perspectives for drug-loaded MSC-derived exosomes in efficiently targeting primary tumors and metastases by reducing side effects. |
topic |
therapeutic exosomes mesenchymal stem cells targeted therapy cancer cells tumor therapy |
url |
https://www.mdpi.com/2072-6694/11/6/798 |
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