Transferrin-Conjugated pH-Responsive ?-Cyclodextrin Nanoparticles for Antitumoral Topotecan Delivery.
ABSTRACT: In this study, we developed ?-cyclodextrin-based multifunctional nanoparticles (NPs) for tumor-targeted therapy. The NPs were self-assembled using a ?-cyclodextrin (?CD) coupled with phenylacetic acid (PA), 2,3-dimethylmaleic anhydride (DMA), poly(ethylene glycol) (PEG), and transferrin (Tf), termed ?CDP-(DMA/PEG-Tf) NPs. These ?CDP-(DMA/PEG-Tf) NPs are effective in entrapping topotecan (TPT, as a model antitumor drug) resulting from the ionic interaction between pH-responsive DMA and TPT or the host-guest interaction between ?CDP and TPT. More importantly, the ?CDP-(DMA/PEG-Tf) NPs can induce ionic repulsion at an endosomal pH (~6.0) resulting from the chemical detachment of DMA from ?CDP, which is followed by extensive TPT release. We demonstrated that ?CDP-(DMA/PEG-Tf) NPs led to a significant increase in cellular uptake and MDA-MB-231 tumor cell death. In vivo animal studies using an MDA-MB-231 tumor xenografted mice model supported the finding that ?CDP-(DMA/PEG-Tf) NPs are effective carriers of TPT to Tf receptor-positive MDA-MB-231 tumor cells, promoting drug uptake into the tumors through the Tf ligand-mediated endocytic pathway and increasing their toxicity due to DMA-mediated cytosolic TPT delivery.
PROVIDER: S-EPMC7698888 | BioStudies |