Engineering extracellular vesicles derived from lemons for delivering chemotherapeutic drug employing periostin targeting

Abstract

Drug administration methods aim to reduce adverse effects and enhance the effectiveness of chemotherapy medications. Extracellular vesicles (EVs) have shown outstanding ability in drug delivery for a wide range of drugs, including chemotherapy drugs. One of the main objectives of this study was to enhance the selective delivery of doxorubicin (DOX) by utilizing modified lemon extracellular vesicles (LEV) for targeted delivery, in order to overcome breast cancer. Additionally, it aimed to further hinder both cancer cell growth and movement by disrupting periostin peptide (PN) via interaction between anti-periostin peptide (APN) and PN. The LEV was extracted from lemon juice, modified with APN onto its surface, and then DOX was loaded into the LEV-APN. The particle size and zeta potential were measured. The release study of DOX from the LEV-APN-DOX nanodrug was higher at an acidic pH 5.4 than the normal pH 7.4. The cellular uptake and cytotoxicity of the LEV-APN-DOX nanodrug were evaluated using flow cytometry analysis and the MTT method, respectively. In vivo therapeutic efficiency of the prepared nanoformulation was assessed using 4T1 tumor-bearing female BALB/c mice. Ex vivo fluorescent imaging revealed increased tumor accumulation and decreased heart clearance in LEV-APN-DOX compared to DOX. The histopathological evaluation also confirmed this result. Our findings highlight the potential of utilizing APN-modified liposomal doxorubicin to specifically target and efficiently treat breast adenocarcinoma.