Development and in vitro evaluation of pH-sensitive naringenin@ZIF-8 polymeric micelles mediated by aptamer

In this study, a pH-sensitive and aptamer-modified drug-loading polymer micelles were designed and synthesized based on the natural plant extract of naringenin(NAR), and further evaluated the drug delivery system in vitro. First of all, the optimal preparation process of (NAR@ZIF-8)/PMs was obtained by Box-Behnken effect surface method. It showed that the regular spherical shape and good dispersion with the transmission electron microscope (TEM). More specifically, the particle size was 239.8 +/- 0.76 nm. The zeta potential was -8.9 +/- 0.14 mV. The release of AP-(NAR@ZIF-8)/PMs was tested in different pH dissolution media, and the results showed that AP-(NAR@ZIF-8)/PMs could be rapidly released 91.4% within 48 h in the dissolution media with pH = 5.0. It indicated AP-(NAR@ZIF-8)/PMs had superior pH-sensitive release ability. Secondly, AP-(NAR@ZIF-8)/PMs modified with aptamers were prepared by coupling reaction. The results of UV spectroscopy, particle size, zeta potential, X-ray diffraction (XRD) and fourier transform infrared spectroscopy (FTIR) all showed that the aptamer AS1411 had been successfully modified on the surface of (NAR@ZIF-8)/PMs. The MTT method was used to study the in vitro anti-tumor effects of AP-(NAR@ZIF-8)/PMs on human lung cancer A549 cells and human breast cancer MCF-7 cells. Cytotoxicity and proliferation tests showed that AP-(NAR@ZIF-8)/PMs had significant inhibitory effects on human lung cancer A549 cells and human breast cancer MCF-7 cells. The MTT tests confirmed AP-(NAR@ZIF-8)/PMs had obvious targeting effect on human lung cancer A549 cells and human breast cancer MCF-7 cells. In conclusion, this study showed that AP-(NAR@ZIF-8)/PMs achieves the synergism of tumor targeting and pH-sensitive drug release, and provides a new idea for the treatment of malignant tumors.

Automated summary

This study successfully synthesized a pH-sensitive and aptamer-modified drug-loading polymer micelles, demonstrating superior tumor targeting and pH-sensitive drug release abilities. In vitro experiments showed significant inhibitory effects and clear targeting of AP-(NAR@ZIF-8)/PMs on human lung cancer and breast cancer cells.