Layered Double Hydroxide-Loaded miR-30a for the Treatment of Breast Cancer In Vitro and In Vivo

MicroRNAs (miRNAs) play an essential role in cancer therapy,butthe disadvantages of its poor inherent stability, rapid clearance,and low delivery efficiency affect the therapeutic efficiency. LoadingmiRNAs by nanoformulations can improve their bioavailability and enhancetherapeutic efficiency, which is an effective miRNA delivery strategy.In this study, we synthesized layered double hydroxides (LDH), whichare widely used as carriers of drugs or genes due to the characteristicsof good biocompatibility, high loading capacity, and pH sensitivity.We loaded the suppressor oncogene miR-30a on LDH nanomaterials (LDH@miR-30a)and determined the mass ratio of miRNA binding to LDH by agarose gelelectrophoresis. LDH@miR-30a was able to escape the lysosomal pathwayand was successfully phagocytosed by breast cancer SKBR3 cells andremained detectable in the cells after 24 h of co-incubation. In vitroexperiments showed that LDH@miR-30a-treated SKBR3 cells showed decreasedproliferation and cell cycle arrest in the G0/G1 phase and LDH@miR-30awas able to regulate the epithelial-mesenchymal transition(EMT) process and inhibit cell migration and invasion by targetingSNAI1. Meanwhile, in vivo experiments showed that nude mice treatedwith LDH@miR-30a showed a significant reduction in their solid tumorsand no significant impairment of vital organs was observed. In conclusion,LDH@miR-30a is an effective drug delivery system for the treatmentof breast cancer.

Automated summary

In this study, layered double hydroxides (LDH) nanomaterials were synthesized and used as carriers to deliver the suppressor oncogene miR-30a for breast cancer therapy. LDH@miR30a was able to escape the lysosomal pathway, be phagocytosed by breast cancer cells, and remain stable in the cells. In vitro experiments showed that LDH@miR30a inhibited proliferation and induced cell cycle arrest in breast cancer cells, as well as regulated the EMT process and inhibited cell migration and invasion. In vivo experiments demonstrated that LDH@miR30a treatment significantly reduced solid tumors without causing significant impairment to vital organs. Therefore, LDH@miR30a is an effective drug delivery system for breast cancer treatment.