MicroRNAs (miRNAs) play an essential role in cancer therapy,
but
the disadvantages of its poor inherent stability, rapid clearance,
and low delivery efficiency affect the therapeutic efficiency. Loading
miRNAs by nanoformulations can improve their bioavailability and enhance
therapeutic efficiency, which is an effective miRNA delivery strategy.
In this study, we synthesized layered double hydroxides (LDH), which
are widely used as carriers of drugs or genes due to the characteristics
of 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 gel
electrophoresis. LDH@miR-30a was able to escape the lysosomal pathway
and was successfully phagocytosed by breast cancer SKBR3 cells and
remained detectable in the cells after 24 h of co-incubation. In vitro
experiments showed that LDH@miR-30a-treated SKBR3 cells showed decreased
proliferation and cell cycle arrest in the G0/G1 phase and LDH@miR-30a
was able to regulate the epithelial–mesenchymal transition
(EMT) process and inhibit cell migration and invasion by targeting
SNAI1. Meanwhile, in vivo experiments showed that nude mice treated
with LDH@miR-30a showed a significant reduction in their solid tumors
and no significant impairment of vital organs was observed. In conclusion,
LDH@miR-30a is an effective drug delivery system for the treatment
of breast cancer.
A core feature of liver fibrosis is the activation of hepatic stellate cells (HSCs), which are transformed into myofibroblasts and lead to the accumulation of extracellular matrix (ECM) proteins. In this study, we combined in vitro cellular efficacy with in vivo antifibrosis performance to evaluate the outcome of sorafenib (SRF) loaded layered double hydroxide (LDH) nanocomposite (LDH-SRF) on HSCs. The cellular uptake test has revealed that sorafenib encapsulated LDH nanoparticles were efficiently internalized by the HSC-T6 cells, synergistically inducing apoptosis of hepatic stellate cells. Moreover, the apoptosis rate and the migration inhibition rate induced by LDHs-SRF were 2.5 and 1.7 times that of SRF. Western Blot showed that the TGF-β1/Smad/EMT and AKT signaling pathway was significantly inhibited in HSC-T6 cells treated with LDHs-SRF. For the in vivo experiment, LDHs-SRF were administered to rat models of CCl4-induced liver fibrosis. H&E, masson and sirius red staining showed that LDHs-SRF could significantly reduce inflammatory infiltrate and collagen fiber deposition and immunohistochemical results found that LDHs-SRF treatment significantly inhibited the protein expressions of α-SMA in the liver, these results suggesting that LDHs-SRF exhibited better anti-fibrotic effect than SRF alone and significantly inhibited the proliferation and activation of rat hepatic stellate cells and collagen fiber synthesis.
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