The present invention discloses doxorubicin derivatives for targeted activation by Legumain, its preparation method and use. The doxorubicin derivatives are obtained by condensation between the amino group of compound A and the carboxyl group of compound B and have the following structure:compounds A and B have the following structures, respectively:wherein R3 in compound B is Leu or absent R4 is any one amino acid selected from the group consisting of Ala and Thr R5 is any one amino acid selected from the group consisting of Ala, Thr and Asn R6 iswherein n=1-20 orwherein R7 is substituted or unsubstituted, linear or branched, saturated or unsaturated C1-C20 fatty hydrocarbon, or substituted or unsubstituted C6-C20 aromatic hydrocarbon. The doxorubicin derivatives of the present invention are specifically tumor-targeted and have a long in vivo metabolic half-life, as compared with doxorubicin. They exhibit an efficient and safe anti-tumor effect and could be used to prepare an anti-tumor drug.
