Targeted delivery of doxorubicin using RSV F-protein modified breast cancer-derived exosomes in breast cancer-bearing mice.

Authors

Narges Mardi, Amir Zarebkohan, Cigir Biray-Avci, Reza Rahbarghazi, Mehdi Talebi, Hamid Lotfimehr, Sharareh Khavandkari, Zahra Abbasi-Malati, Nastaran Sedghi-Samarkhazan, Elham Shahriyari, Asghar Khalilnezhad, Morteza Milani, Mohammad Nouri

Published in

BioImpacts : BI. Volume 16. Pages 33180. Epub Jun 15, 2026.

Abstract

Triple-negative breast cancer demonstrated high metastasis and mortality rates in female populations. Emerging data on effective targeting and specific internalization of chemotherapeutic agents, using modified exosomes, decreased the therapeutic dosage of anti-cancer drugs in cancer cells.
Herein, we developed modified exosomes by surface decoration using the Fusion protein of Respiratory Syncytial Virus (F-protein of RSV) through Click-chemistry techniques, and Dox-loaded via sonication strategy. Then, the viability and metastatic behaviors of MDA-MB-231 cells were monitored in the presence of different groups, including Dox, Exosomes (Exo), Exosomes loaded with Dox (Exo@Dox), and F-protein coupled Exosome groups (Exo-F) and (Exo-F@Dox).
In vitro and in vivo results verified that the F-protein coupled exosome, as a modified natural nanoplatform, possessed a biocompatible nature in blood circulation and crossing of blood barriers. After exposure to tumoral temperature (40 °C) and lysosomal PH (5.5) demonstrate amplified Dox release (around 60% at 8 h). Also, in vitro uptake results confirmed a significant increase in Exo-F internalization compared to the Exo group in MDA-MB-231 cells (P<0.0001). Correspondingly, the IC50 value of Exo-F@Dox versus free Dox showed a significant reduction (24-fold more potent) (P<0.0001). Interestingly, Dox-free modified Exo (Exo-F) showed appreciable cytotoxicity (IC50 of about 0.1 µg /mL for exosomal protein concentration) (P˂0.0001). Also, migration assay results confirmed a considerable decrease in the migrated population of MDA-MB-231 cells (10%) compared to the control group, following exposure to modified exosomes. Interestingly, an in vivo study in tumor-bearing Balb/c mice demonstrated a significantly decreased tumor size in the Exo-F groups compared to other formulations.
In summary, F-protein modified exosomes exhibited superior anticancer efficacy by improving tumor-specific targeting, ensuring precise delivery of chemotherapeutic agents, facilitating efficient drug release, and allowing for lower therapeutic dosages.

PMID:
42371526
Bibliographic data and abstract were imported from PubMed on 29 Jun 2026.

Read full publication at:
Please sign in to see all details.

Stats

1-terrible, 9-excellent. How would you rate this publication? Sign in in to submit your rating.

Post a comment

You need to be signed in to post comments. You can sign in here.

Comments

There are no comments yet.