Dual-Targeted Controlled Delivery Based on Folic Acid Modified Pectin-Based Nanoparticles for Combination Therapy of Liver Cancer

Dihydroartemisinin (DHA) as an effective anticancer drug is being concerned owing to the excellent efficacy, but the poor solubility and premature release confine the clinical application. Construction of a satisfied DHA-loaded delivery system with targeted recognition and specific controlled release brings opportunities and challenges, which can be triggered through an endogenous stimulus. In this work, we designed a traceable and dual-targeted DHA-loaded nanocarrier by taking advantage of the highly expression of pectin with galactose residues to asialoglycoprotein receptors on the surface of liver, as well as the highly expression of folic acid (FA) to folic acid receptors. Folic acid modified pectin was coupled with DHA-loaded eight-arm polyethylene glycol conjugates to prepare folic acid-pectin-eight arm polyethylene glycol-dihydroartemisinin prodrugs (FA-Pectin-8armPEG-DHA), and then embedded hydroxycamptothecin by the self-assembly of hydrophobic drugs and hydrophilic carriers to prepare folic acid-pectin-eight-arm polyethylene glycol-dihydroartemisinin/hydroxycamptothecin nanoparticles (FPPDH NPs). FPPDH NPs showed an average particle size 98 nm under maximum drug loading (7.04 wt %) and encapsulation efficiency (20.57 wt %). The enhanced cytotoxicity of FPPDH NPs were 204.5-fold (H22) and 178.4-fold (HepG2) to the free DHA, respectively. In addition, a clear synergy of drugs suggested that the dual-targeted combination therapy is a reliable therapeutic strategy.