Amphiphilic drug-drug conjugate for cancer therapy with combination of chemotherapeutic and antiangiogenesis drugs

The progression and metastasis of solid tumors strongly rely on the process of forming nascent blood vessels. However, using angiogenesis inhibitors alone does not meet the cancer treatment needs. Herein, we used the amphiphilic drug-drug conjugate (ADDC) strategy to fabricate a new drug conjugate with the combination of chemotherapeutic drug and antiangiogenesis drug together. With one-step esterification of hydrophilic floxuridine (FUDR) and hydrophobic pseudolaric acid B (PAB), the conjugate was synthesized. The amphiphilic property of FUDR-PAB conjugate induced the self-assembly to form nanoparticles in water. From further in vitro and in vivo experiments, this FUDR-PAB conjugate does not only have a high antitumor effect, but also shows efficient antianiogenesis property. These results offer a promising ADDC strategy for designing drugs with combination of chemotherapeutic drug and antiangiogenesis drug together.