Synthesis of an amphiphilic bi-prodrug based on gossypol and cytarabine for drug self-delivery

Drug–drug conjugates have become a research hotspot in nanomedicine. An amphiphilic assembled drug–drug conjugate can achieve drug self-delivery without any carriers and change the distribution of free drugs. Herein, we synthesized a pH-responsive bi-prodrug of gossypol (GP) and cytarabine (Ara-C) for cancer therapy. FT-IR, UV-vis, TLC and MS confirmed that GP-Ara-C was successfully synthesized. The nanoparticle size of GP-Ara-C is approximately 100 nm, and the stability of GP-Ara-C is maintained for 6 days in pH 7.4 phosphate-buffered saline (PBS). HeLa cell viability results showed that GP-Ara-C exhibited anticancer ability similar to that of free GP. Cellular uptake demonstrated that GP-Ara-C could be distributed in cell nuclei at 7 h. Altogether, this amphiphilic GP-Ara-C could be assembled into nanomedicine in an aqueous environment and could be a candidate for cancer therapy in clinics.