Abstract
Extracellular vesicles (EVs) are an experimental class of drug carriers. Alternative sources of EVs are currently being explored to overcome limitations related to their manufacturing from mesenchymal stem cells. In this work, Citrus limon-derived EVs were tested as carriers for the widely used chemotherapeutic drug - doxorubicin (DOX). Capillary electrophoresis (CE) and nanoplasmonic sensing (NPS) were developed for the quality control of DOX-EV preparations. It was found that the CE method enables simultaneous detection of free and incorporated DOX and allows assessing the stability of the preparations and the drug leakage. NPS, on the other hand, demonstrated that DOX is accumulated in the interfacial region of the carrier. The activity of DOX-loaded EVs was tested on HeLa (cervical cancer cells) and HEK293T (human embryonic kidney cells) cell lines. It was found that DOX incorporation into plant-derived EVs virtually does not affect the drug's cytotoxicity to HeLa cells but significantly decreases DOX activity against HEK293T cell line.
Keywords:
Capillary electrophoresis; drug incorporation; exosome-like vesicles; extracellular vesicles; nanocarriers; nanoplasmonic sensing.
MeSH terms
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Antibiotics, Antineoplastic / administration & dosage
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Antibiotics, Antineoplastic / pharmacokinetics
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Antibiotics, Antineoplastic / pharmacology
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Cell Survival / drug effects
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Citrus* / chemistry
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Doxorubicin* / administration & dosage
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Doxorubicin* / pharmacokinetics
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Doxorubicin* / pharmacology
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Drug Carriers* / chemistry
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Extracellular Vesicles / chemistry
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Extracellular Vesicles / metabolism
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HEK293 Cells
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HeLa Cells
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Humans
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Nanoparticles / chemistry
Substances
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Doxorubicin
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Drug Carriers
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Antibiotics, Antineoplastic
Grants and funding
The studies were supported by the National Science Centre (A.S. by Grant No. 2022/45/N/NZ7/01417) and by the Polish Ministry of Education and Science (A.S. by Grant No. 533/71/01419/0004717; S.D. by Grant No. 514/61/71-01415/0004590; A.P. and L.K. by Grant No. 2/566516/SPUB/SP/2023). The authors further acknowledge funding from NordForsk for the Nordic University Hub Project No. 85352 (Nordic POP, Patient Oriented Products). A.H. and G.S.C. acknowledge funding by the LEO Foundation (Grant No. LF15007 and LF-ST-21-500005 Project 1). Financial support from the Finnish Society of Sciences and Letters under Grant Number 4709946 (S.K.W.) and from the Waldemar von Frenckell’s Foundation under Grant Number 4706562 (S.K.W.) are acknowledged.