Self-assembled nanoparticles based on a carboxymethylcellulose-ursolic acid conjugate for anticancer combination therapy

A new self-assembled nanoparticle platform based on a carboxymethylcellulose (CMC)-ursolic acid (UA) conjugate is presented for the first time. The CMC-UA conjugate was synthesized by introducing the hydrophobic drug UA into the hydrophilic polymer molecule CMC, and then another anticancer drug, hydroxycamptothecin (HCPT), was encapsulated into the self-assembled nanoparticles (CMC-UA/HCPT NPs) of the conjugate formed by the nanoprecipitation method. The obtained nanoparticles possessed appropriate size (similar to 40 nm), high encapsulation efficiency (similar to 17.53 wt% HCPT) and drug-loading efficiency (similar to 29.62 wt% UA). Cell experiments indicated that CMC-UA/HCPT NPs exhibited higher cytotoxicity than free UA and free HCPT, owing to the longer blood retention time than free drug (7.3-fold UA, 2.5-fold HCPT) and effective cellular uptake. Anti-tumor capacity, mice survival rate and tumor growth inhibition of UA and HCPT were also significant. Moreover, the evaluation of the side effects clearly and elaborately certified that NPs could reduce the risk of hypersensitivity reactions substantially. Therefore, CMC-UA/HCPT NPs is a further prospective anticancer drug delivery system.