A Novel Tumor-Targeting Drug-Delivery System of Docetaxel-Loaded Poly(β-hydroxybutyrate) Nanoparticles Binding with a...

Tumor cells maintain rapid proliferation based on their highly increasing energy metabolism. Therefore, glucose-related energy substrate control therapy may become a promising approach for cancer treatment. Based on the specific binding capacity of Pisum sativum agglutinin (PSA) to glucose, a novel sugar-mediated tumor-targeting drug-delivery system was designed, constructed, and characterized in this study. An antitumor drug of docetaxel (DTX) was encapsulated into poly-(β-hydroxybutyrate) (PHB) nanoparticles by ultrasonic emulsification and solvent evaporation method to construct PHB-DTX-NPs. Then, PSA was anchored onto the prepared PHB-DTX-NPs to construct PSA-PHB-DTX-NPs (213.07 nm, -1.28 mV). In vitro retarded DTX release (46.98%) from PSA-PHB-DTX-NPs with sugar-binding specificity was triggered by glucose and increased to 98.27% within 9 days. PSA-PHB-DTX-NPs exhibited effective cell uptake and cytotoxicity to MCF-7 breast cancer cells. In vivo imaging system images showed that agglutinin NPs target the tumor tissue and preferentially distribute at the tumor site of MCF-7-bearing nude mice. After administration, the decreased tumor size indicated the inhibition of tumor progression and a significant antitumor effect (inhibitory rate of 97.06%) with negligible system toxicity. Further results from an in vivo pharmacokinetics study demonstrated that PSA-PHB-DTX-NPs could effectively increase the drug concentration and prolong the circulation time in blood, which contributed to the greatly enhanced antitumor efficiency. Hence, PSA-PHB-DTX-NPs could serve as a tumor-targeted drug-delivery system, offering novel insights for glucose-mediated cancer therapy.