Folate-Targeted pH and Redox Dual Stimulation-Responsive Nanocarrier for Codelivering of Docetaxel and TFPI-2 for Nasopharyngeal Carcinoma Therapy.

Abstract

Due to the increasing incidence of tumor metastasis and multidrug resistance, even though a combined use of chemotherapy and radiotherapy is introduced, the 5-year average survival rate of an advanced nasopharyngeal carcinoma (NPC) patient still remains low. Hence, targeted slow-release anticancer drugs represent a potential therapy for advanced NPC. In this study, pH and redox dual stimulation-responsive folate-targeted folic acid - β-cyclodextrin - hyperbranched poly(amido amine)s (FA-DS-PAAs) nanocarriers for codelivery of docetaxel (DOC) and tissue factor pathway inhibitor 2 (TFPI-2) for NPC therapy are discussed. Physical and chemical properties, in vitro DOC-release properties, folic acid (FA)-targeting, transfection, Western blotting, DOC and TFPI-2 codelivery, therapeutic properties, targeted inhibition, and biocompatibility, in vivo FA-targeting, toxicity, and therapeutic properties of FA-DS-PAAs/DOC/TFPI2 nanoparticles are evaluated. The results indicate that the 200 nm low-toxicity FA-DS-PAAs/DOC/TFPI2 nanoparticles could enhance TFPI2 gene expression, make cancer cells more sensitive to DOC, induce cell apoptosis, and reduce cell invasion more effectively compared with monochemotherapy. With respect to the targeted release of drugs (DOC and TFPI2) in tumor cells, FA-DS-PAAs/DOC/TFPI2 is associated with the slowest growth rate of tumor and the smallest volume of tumor, so this study demonstrates the best synergetic antitumor effect. We anticipate that this study is important because it not only provides a potential new therapy approach for NPC but also paves the preclinical way for potential application of FA-DS-PAAs/DOC/TFPI2.