Novel Paclitaxel-Loaded Nanoparticles Based on Human H Chain Ferritin for Tumor-Targeted Delivery

Abstract

Paclitaxel (PTX), an excellent chemotherapeutic antitumor drug, is widely used to treat patients with various cancers. However, its clinical applications are greatly restricted by poor solubility and lack of targeting. Herein, we applied natural human H chain ferritin (HFtn) nanocages that can bind to tumor cells via interacting with the human transferritin receptor 1 (TfR1) leading to its endocytosis as the PTX carrier for the targeted delivery. PTX molecules were encapsulated into HFtn cavity using disassembly/reassembly method through adjusting pH. According to the requirements of drugs suitable for clinical trials, HFtn can be easily purified in high yields with no ligand modification or property modulation. We demonstrated that PTX molecules were successfully encapsulated in the protein nanocages. The HFtn-PTX nanoparticles exhibited similar morphology and structural characteristics to the hollow cage and showed significant cytotoxicity in vitro than the naked PTX. Flow cytometry, confocal laser scanning microscopy, and in vivo imaging of MDA-MB-231 tumor demonstrated the HFtn-PTX nanoparticles targeting ability to tumor cells. Cell apoptosis assay showed that HFtn-PTX had similar apoptotic characteristics on MDA-MB-231 cells as that of the free PTX. HFtn-PTX nanoparticles have higher in vivo therapeutic efficacy and lower systemic toxicity. The BALB/c mice model also confirmed the effectiveness of the nanoparticles. Specifically targeting to tumors and solving the solubility issue of water-insoluble drugs thus alleviating the side effects, HFtn can be an efficient hydrophobic drug delivery nanocarrier for further applications in cancer therapy.