Phenylboronic acid-modified polymaleic anhydride-F127 micelles for pH-activated targeting delivery of doxorubicin

Phenylboronic acid (PBA) is a tumor-targeting molecule which selectively recognizes sialic acid (SA) overexpressed in tumors. In the study, PBA, F127 and ethanolamine were conjugated with poly(maleic anhydride) by one-step reaction to form amphiphilic polymer for doxorubicin encapsulation. Two drug-carrying micelles with different mass ratio of polymer to drug were prepared by dialysis method to study effect of PBA on doxorubicin release, tumor-targeting and antitumor activity. The study results showed that doxorubicin release from the formulations was acid-sensitive and affected by the polymer dosage, and its acid-induced release behavior improved its insertion into DNA base pairs. Formulation with high polymer dosage showed better tumor targeting and antitumor activity, and activity of inhibiting HepG2 with higher content of SA-containing glycosphingolipids was higher than that of anti-B16. In vivo studies on the activity of B16-bearing mice showed that the doxorubicin-loaded micelles could inhibit the tumor growth and were safer than free doxorubicin. Thus, the PBA-modified nano-polymer micelles have potential biomedical applications due to their nanostructure and tumor-targeting ability.