Enhanced in vitro and in vivo therapeutic efficacy of codrug-loaded nanoparticles against liver cancer

摘要

Paclitaxel (Ptx), one of the most widely used anticancer agents, has demonstrated extraordinary activities against a variety of solid tumors. However, the therapeutic response of Ptx is often associated with severe side effects caused by its nonspecific cytotoxic effects and special solvents (Cremophor EL^®). The current study reports the stable controlled release of Ptx/tetrandrine (Tet)-coloaded nanoparticles by amphilic methoxy poly(ethylene glycol)–poly(caprolactone) block copolymers. There were three significant findings. Firstly, Tet could effectively stabilize Ptx-loaded nanoparticles with the coencapsulation of Tet and Ptx. The influence of different Ptx/Tet feeding ratios on the size and loading efficiency of the nanoparticles was also explored. Secondly, the encapsulation of Tet and Ptx into nanoparticles retains the synergistic anticancer efficiency of Tet and Ptx against mice hepatoma H22 cells. Thirdly, in the in vivo evaluation, intratumoral administration was adopted to increase the site-specific delivery. Ptx/Tet nanoparticles, when delivered intratumorally, exhibited significantly improved antitumor efficacy; moreover, they substantially increased the overall survival in an established H22-transplanted mice model. Further investigation into the anticancer mechanisms of this nanodelivery system is under active consideration as a part of this ongoing research. The results suggest that Ptx/Tet-coloaded nanoparticles could be a potential useful chemotherapeutic formulation for liver cancer therapy.