Cargando…
Pancreatic Ductal Cell-Derived Extracellular Vesicles Are Effective Drug Carriers to Enhance Paclitaxel’s Efficacy in Pancreatic Cancer Cells through Clathrin-Mediated Endocytosis
Chemo-resistance challenges the clinical management of pancreatic ductal adenocarcinoma (PDAC). A limited admittance of chemotherapeutics to PDAC tissues is a key obstacle in chemotherapy of the malignancy. An enhanced uptake of drugs into PDAC cells is required for a more effective treatment. Extra...
Autores principales: | , , , , |
---|---|
Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
MDPI
2022
|
Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9099870/ https://www.ncbi.nlm.nih.gov/pubmed/35563165 http://dx.doi.org/10.3390/ijms23094773 |
_version_ | 1784706713292636160 |
---|---|
author | Sun, Haoyao Bhandari, Kritisha Burrola, Stephanie Wu, Jinchang Ding, Wei-Qun |
author_facet | Sun, Haoyao Bhandari, Kritisha Burrola, Stephanie Wu, Jinchang Ding, Wei-Qun |
author_sort | Sun, Haoyao |
collection | PubMed |
description | Chemo-resistance challenges the clinical management of pancreatic ductal adenocarcinoma (PDAC). A limited admittance of chemotherapeutics to PDAC tissues is a key obstacle in chemotherapy of the malignancy. An enhanced uptake of drugs into PDAC cells is required for a more effective treatment. Extracellular vesicles (EVs), especially small EVs (sEVs), have emerged as drug carriers for delivering chemotherapeutics due to their low immunogenicity and propensity for homing toward tumor cells. The present study evaluated sEVs derived from six different human cell lines as carriers for paclitaxel (PTX). The encapsulation of the chemotherapeutics was achieved using incubation, sonication and electroporation. The cytotoxicity of the EV drugs was evaluated by MTS assay. While sonication led to a higher efficiency of drug loading than incubation and electroporation, PTX loaded through incubation with HPNE-derived sEVs (HI-PTX) was the most efficacious in killing PDAC cells. Furthermore, HI-PTX was taken up by PDAC cells more efficiently than other EV drugs, implying that the efficacy of HI-PTX is associated with its efficient uptake. This was supported by the observation that the cytotoxicity and uptake of HI-PTX is mediated via the clathrin-dependent endocytosis. Our results indicate that the hTERT-HPNE cell-derived EVs are effective drug carriers to enhance paclitaxel’s efficacy in PDAC cells. |
format | Online Article Text |
id | pubmed-9099870 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
spelling | pubmed-90998702022-05-14 Pancreatic Ductal Cell-Derived Extracellular Vesicles Are Effective Drug Carriers to Enhance Paclitaxel’s Efficacy in Pancreatic Cancer Cells through Clathrin-Mediated Endocytosis Sun, Haoyao Bhandari, Kritisha Burrola, Stephanie Wu, Jinchang Ding, Wei-Qun Int J Mol Sci Article Chemo-resistance challenges the clinical management of pancreatic ductal adenocarcinoma (PDAC). A limited admittance of chemotherapeutics to PDAC tissues is a key obstacle in chemotherapy of the malignancy. An enhanced uptake of drugs into PDAC cells is required for a more effective treatment. Extracellular vesicles (EVs), especially small EVs (sEVs), have emerged as drug carriers for delivering chemotherapeutics due to their low immunogenicity and propensity for homing toward tumor cells. The present study evaluated sEVs derived from six different human cell lines as carriers for paclitaxel (PTX). The encapsulation of the chemotherapeutics was achieved using incubation, sonication and electroporation. The cytotoxicity of the EV drugs was evaluated by MTS assay. While sonication led to a higher efficiency of drug loading than incubation and electroporation, PTX loaded through incubation with HPNE-derived sEVs (HI-PTX) was the most efficacious in killing PDAC cells. Furthermore, HI-PTX was taken up by PDAC cells more efficiently than other EV drugs, implying that the efficacy of HI-PTX is associated with its efficient uptake. This was supported by the observation that the cytotoxicity and uptake of HI-PTX is mediated via the clathrin-dependent endocytosis. Our results indicate that the hTERT-HPNE cell-derived EVs are effective drug carriers to enhance paclitaxel’s efficacy in PDAC cells. MDPI 2022-04-26 /pmc/articles/PMC9099870/ /pubmed/35563165 http://dx.doi.org/10.3390/ijms23094773 Text en © 2022 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/). |
spellingShingle | Article Sun, Haoyao Bhandari, Kritisha Burrola, Stephanie Wu, Jinchang Ding, Wei-Qun Pancreatic Ductal Cell-Derived Extracellular Vesicles Are Effective Drug Carriers to Enhance Paclitaxel’s Efficacy in Pancreatic Cancer Cells through Clathrin-Mediated Endocytosis |
title | Pancreatic Ductal Cell-Derived Extracellular Vesicles Are Effective Drug Carriers to Enhance Paclitaxel’s Efficacy in Pancreatic Cancer Cells through Clathrin-Mediated Endocytosis |
title_full | Pancreatic Ductal Cell-Derived Extracellular Vesicles Are Effective Drug Carriers to Enhance Paclitaxel’s Efficacy in Pancreatic Cancer Cells through Clathrin-Mediated Endocytosis |
title_fullStr | Pancreatic Ductal Cell-Derived Extracellular Vesicles Are Effective Drug Carriers to Enhance Paclitaxel’s Efficacy in Pancreatic Cancer Cells through Clathrin-Mediated Endocytosis |
title_full_unstemmed | Pancreatic Ductal Cell-Derived Extracellular Vesicles Are Effective Drug Carriers to Enhance Paclitaxel’s Efficacy in Pancreatic Cancer Cells through Clathrin-Mediated Endocytosis |
title_short | Pancreatic Ductal Cell-Derived Extracellular Vesicles Are Effective Drug Carriers to Enhance Paclitaxel’s Efficacy in Pancreatic Cancer Cells through Clathrin-Mediated Endocytosis |
title_sort | pancreatic ductal cell-derived extracellular vesicles are effective drug carriers to enhance paclitaxel’s efficacy in pancreatic cancer cells through clathrin-mediated endocytosis |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9099870/ https://www.ncbi.nlm.nih.gov/pubmed/35563165 http://dx.doi.org/10.3390/ijms23094773 |
work_keys_str_mv | AT sunhaoyao pancreaticductalcellderivedextracellularvesiclesareeffectivedrugcarrierstoenhancepaclitaxelsefficacyinpancreaticcancercellsthroughclathrinmediatedendocytosis AT bhandarikritisha pancreaticductalcellderivedextracellularvesiclesareeffectivedrugcarrierstoenhancepaclitaxelsefficacyinpancreaticcancercellsthroughclathrinmediatedendocytosis AT burrolastephanie pancreaticductalcellderivedextracellularvesiclesareeffectivedrugcarrierstoenhancepaclitaxelsefficacyinpancreaticcancercellsthroughclathrinmediatedendocytosis AT wujinchang pancreaticductalcellderivedextracellularvesiclesareeffectivedrugcarrierstoenhancepaclitaxelsefficacyinpancreaticcancercellsthroughclathrinmediatedendocytosis AT dingweiqun pancreaticductalcellderivedextracellularvesiclesareeffectivedrugcarrierstoenhancepaclitaxelsefficacyinpancreaticcancercellsthroughclathrinmediatedendocytosis |