Preparation and biological evaluation of antibody targeted metal-organic framework drug delivery system (TDDS) in Her2 receptor-positive cells

Abstract

In this study, we designed and prepared a trastuzumab-coupled drug delivery system with pH response characteristics using mesoporous zeolitic imidazolate framework-8 (ZIF-8) as the carrier, Trastuzumab@ZIF-8@DOX. As results, the targeted drug delivery system (TDDS) ultimately showed high drug loading and good biocompatibility. The cumulative curve of drug release indicated that the early leakage levels were low under neutral pH conditions. However, under acidic pH conditions, there was an effective enhancement in drug release, indicating the presence of an explicit pH-triggered drug release mechanism. The results indicate that the prepared nanoparticles have the potential to serve as drug delivery systems, as they can release the loaded drug in a controlled manner. The results of cellular uptake tests showed that the uptake of the nanoparticles was greatly enhanced by the internalization mediated by the HER2 antibody. This finding indicates that the prepared nanoparticles can selectively target cancer cells that overexpress HER2. When the doxorubicin dose was 5 μg/ml, the survival rate of SK-BR-3 cells (cancer cells) was 47.75 %, and the survival rate of HaCaT cells (healthy cells) was 75.25 % when co-cultured with both cells. The therapeutic efficacy of Trastuzumab@ZIF-8@DOX was assessed on BALB/c nude mice to validate its potential as an effective drug delivery system for tumor inhibition in vivo. In conclusion, these findings demonstrate the specificity-targeted and pH-responsive nature of this smart drug delivery system, highlighting its promising prospects for efficient and controllable cancer treatment applications.