Autologous cell-derived exosomes as precision nanocarriers for enhanced targeted drug delivery and therapeutic efficacy in parental tumor cells

Exosomes are emerging as biologically derived nanocarriers for targeted drug delivery. In this study, we compared autologous and heterologous exosomes for delivery of chemotherapeutic agents and ICAM-1 siRNA in lung adenocarcinoma (A549) and brain endothelial (bEND.3) cells. Fluorescence imaging and flow cytometry showed significantly greater uptake of autologous exosomes in parental cells (p < 0.05). Doxorubicin-loaded autologous exosomes reduced A549 viability to 40.5 ± 2.0% at 200 µg/mL, compared to 64.5 ± 8.1% with heterologous exosomes, with similar trends for methotrexate and paclitaxel. Optimised exosome–Lipofectamine–siRNA formulations achieved 49.0 ± 7.2% ICAM-1 knockdown, outperforming controls. Both exosome types were nanosized (34.5 ± 1.0 nm and 72.1 ± 3.3 nm) and expressed CD63, CD81, ALIX, and TSG101. Proteomic analysis revealed a shared core proteome with distinct cell-specific signatures. These findings highlight the superior delivery efficiency of autologous exosomes as precision nanocarriers.