Photoactivatable Prodrug of Doxazolidine Targeting Exosomes

Natural
lipid nanocarriers, exosomes, carry cell-signaling materials
such as DNA and RNA for intercellular communications. Exosomes derived
from cancer cells contribute to the progression and metastasis of
cancer cells by transferring oncogenic signaling molecules to neighboring
and remote premetastatic sites. Therefore, applying the unique properties
of exosomes for cancer therapy has been expected in science, medicine,
and drug discovery fields. Herein, we report that an exosome-targeting
prodrug system, designated MARCKS–ED–photodoxaz, could
spatiotemporally control the activation of an exquisitely cytotoxic
agent, doxazolidine (doxaz), with UV light. The MARCKS–ED peptide
enters a cell by forming a complex with the exosomes in situ at its
plasma membrane and in the media. MARCKS–ED–photodoxaz
releases doxaz under near-UV irradiation to inhibit cell growth with
low nanomolar IC50 values. The MARCKS–ED–photodoxaz
system targeting exosomes and utilizing photochemistry will potentially
provide a new approach for the treatment of cancer, especially for
highly progressive and invasive metastatic cancers.