Effect of Polyamidoamine-Dendrimer Nanoparticles Combined with Human Umbilical Vein Endothelial Cell Microenvironment on the Growth and Immune Infiltration of Nasopharyngeal Carcinoma Cell Line CNE-1

Abstract

In tumor immunotherapy, Treg cells are immune suppressor cells that are difficult to completely eliminate. To address this issue, a nano-delivery system needs to be designed that includes chemotherapeutic agents and multidrug resistance reversal agents to achieve a cascade of immune chemotherapy enhancement. In this study, polyamidoamine-dendrimer (PAMAM) was utilized as the raw material to prepare a dual-sensitive nano-carrier that is both pH and reduction responsive, and loaded with the chemotherapeutic drug doxorubicin (DOX) and the multidrug resistance reversal agent, elacridar (ELC), to generate YPAMAM nanoparticles. Physicochemical property analysis was performed, and the effect of the nanoparticles on extracellular anti-angiogenesis was examined using human umbilical vein endothelial cells (HUVEC). A culture microenvironment was established using human nasopharyngeal carcinoma cells (CNE-1) and YPAMAM-HUVEC, which was rolled into three groups: 100% CNE-1 supernatant (group A), 50% HUVEC-YPAMAM (5:1) supernatant+50% CNE-1 supernatant (group B), and 100% HUVEC-YPAMAM (5:1) supernatant (group C). The effect of each group on the growth and immune infiltration of CNE-1 cells was analyzed. Fourier-transform infrared spectroscopy (FTIR) showed that the nano-carrier was successfully synthesized, and the particle size of the nanoparticles with various DOX/ELC ratios ranged between 10–20 nm. The prepared nanoparticles exhibited high encapsulation efficiency and simultaneous release of both drugs, with a clear reduction and pH sensitivity. Furthermore, nanoparticles applied to HUVEC could promote vascular rupture, and fluorescence staining showed that the microenvironment could reduce VEGF level and inhibit tumor metastasis. The CNE-1 cell adhesion rate and proliferation rate of groups B and C were dramatically inferior to those of group A (P <0.01). Comparison of the various tumor tissue extract groups indicated that the established microenvironment could inhibit the infiltration of CNE-1 cells in tissue, thereby demonstrating that the constructed microenvironment can improve the immunosuppressive effect of tumors.