Delivery of miRNAs through Metal–Organic Framework Nanoparticles for Assisting Neural Stem Cell Therapy for Ischemic Stroke

Abstract

Stroke is the most common cause of disability globally. Neural stem cell (NSC) therapy, which can replace lost and damaged neurons, has been proposed as a potential treatment for stroke. The therapeutic efficacy of NSC therapy is hindered by the fact that only a small number of NSCs undergo neuronal differentiation. Neuron-specific miR-124, which promotes the differentiation of NSCs into mature neurons, can be combined with NSC therapy to cure ischemic stroke. However, the instability and poor internalization of miR-124 seriously hamper its broad clinical application. Herein, an innovative strategy involving delivery of miR-124 via a Ca-MOF@miR-124 nanodelivery system, which effectively prevents the degradation of miR-124 by nucleases and promotes the internalization of miR-124 by NSCs, is presented. The effect of accelerated neuronal directed differentiation of NSCs was assessed through in vitro cell experiments, and the clinical application potential of this nanodelivery system for the treatment of ischemic stroke was assessed through in vivo experiments involving the combination of NSC therapy and Ca-MOF@miR-124 nanoparticles. The results indicate that Ca-MOF@miR-124 nanoparticles can promote the differentiation of NSCs into mature neurons with electrophysiological function within 5 days. The differentiation rate of cells treated with Ca-MOF@miR-124 nanoparticles was at least 5 days faster than that of untreated cells. Moreover, Ca-MOF@miR-124 nanoparticles decreased the ischemic area to almost normal levels by day 7. The combination of Ca-MOF@miR-124 nanoparticles and NSC therapy will enhance the treatment of traumatic nerve injury and neurodegenerative diseases.

Metal‐Organic Frameworks Nanocarriers for Functional Nucleic Acid Delivery in Biomedical Applications

“…Yang et al prepared another nanoparticle Ca-MOF@miR-124, which delivered miR-124 to NSC and promoted the differentiation of mature neurons in NSC. [89] When combined with neural stem cell therapy, it promoted the differentiation of neural stem cells into mature neurons with electrophysiological functions within 5 days in vitro, and reduced the ischemic infarct size to almost normal level in vivo by 7 days. In addition, the system is also applied in treating drug-resistant bacteria.Zhang et al prepared nanoparticles GOx&HRP@ZIF-8/ASO for the treatment of drug-resistant bacteria.…”

Metal‐Organic Framework‐Based Colloidal Particle Synthesis, Assembly, and Application

“…Due to the good cell penetration capacity of F3, these improvements can enhance the accumulation of MOF NPs in cancer cells, exhibiting good tumor‐targeting behavior. In addition, MOF NPs can be used to deliver miRNA to assist neural stem cell therapy of ischemic Stroke [187] or photodynamic therapy treatment of cancer cells [188] …”

Light-Driven and Metal–Organic Framework Synergetic Loaded DNA Tetrahedral Amplifier for Exonuclease III-Powered All-in-One Biosensing and Chemotherapy in Live Biosystems

“…Therefore, a robust carrier to achieve the synergetic loading of the drug is required . Unlike other frequently used biological carrier materials, including inorganic particles, − polymers, , and two-dimensional membranes, − metal–organic frameworks (MOFs) have hollow spaces (pores) for the packaging of the drug and can be easily surface-modified for linkage to the biosensing system. − Even so, there is a risk of the leakage of the drug from the naked porous structure [ i.e. , the surface aperture of UiO-66 (a frequently used MOF) is approximately 2 nm in diameter].…”