Preparation of pH-Sensitive Dextran Nanoparticle for Doxorubicin Delivery

One of challenge for cancer therapy is efficient delivery of anticancer agents into tumor sites to increase efficiency of drugs and reduce side effects. To overcome this challenge, we designed pH-sensitive doxorubicin prodrug (DEX-PEI-DOX) nanoparticles based on dextran-poly(ethylene imine) copolymers (DEX-PEI). The DEX-PEI-DOX conjugates were conveniently prepared by grafting PEI to dextran, and then anticancer drug doxorubicin (DOX) were conjugated to DEX-PEI through acid cleavable cis-aconityl bonds. The experiments of dynamic light scattering (DLS) and transmission electron microscopy (TEM) represented that size of dextran nanoparticles was about 120 nm with uniform spherical shape. In vitro drug release from self-assembled nanoparticles was dependent on the pH of medium due to the cis-aconityl linkage. Confocal images revealed that dextran based pH-sensitive DOX delivery nanoparticle could enter into Human breast carcinoma (MCF-7) cells easily. Therapeutic efficacy against MCF-7 cells in vitro was evaluated through MU assays and the results showed that dextran nanoparticle had obvious anticancer ability. All above results indicated this pH-sensitive DOX-loaded nanoparticles system would be a useful candidate for cancer therapy.