I-motif-coated exosomes as a pH-sensitive carrier for anticancer drugs

Nature-derived exosomes have been noted as emerging carriers for anticancer drugs. In this study, as a proof-of-concept, the anticancer drug doxorubicin (Dox) was loaded onto i-motif-modified exosomes (Exo-i-motif) to deliver Dox to cancer cells efficiently. The double-stranded biotin-i-motif/flare (ds-i-motif-bio)s efficiently released Dox in an acidic pH-responsive manner within 1 h. Based on gel electrophoresis, it was clearly confirmed that ds-i-motif-bio successfully interacts with biotin-conjugated exosomes and streptavidin (strep) via the biotin–streptavidin interaction. The particle sizes were below 150 nm without aggregation after strep-mediated modification of ds-i-motif-bio on the surfaces of the exosomes. In addition, released Dox had intact bioactivity for anti-proliferation after immobilization onto the exosomes. This study could serve as a new concept of pH-responsive delivery systems of anticancer drug using nature-derived exosomes with i-motifs.