Encapsulation of Plasmid DNA by Nanoscale Metal–Organic Frameworks for Efficient Gene Transportation and Expression

Abstract

The intracellular delivery and functionalization of genetic molecules play critical roles in gene‐based theranostics. In particular, the delivery of plasmid DNA (pDNA) with safe nonviral vectors for efficient intracellular gene expression has received increasing attention; however, it still has some limitations. A facile one‐pot method is employed to encapsulate pDNA into zeolitic imidazole framework‐8 (ZIF‐8) and ZIF‐8‐polymer vectors via biomimetic mineralization and coprecipitation. The pDNA molecules are found to be well distributed inside both nanostructures and benefit from their protection against enzymatic degradation. Moreover, through the use of a polyethyleneimine (PEI) 25 kD capping agent, the nanostructures exhibit enhanced loading capacity, better pH responsive release, and stronger binding affinity to pDNA. From in vitro experiments, the cellular uptake and endosomal escape of the protected pDNA are greatly improved with the superior ZIF‐8‐PEI 25 kD vector, leading to successful gene expression with high transfection efficacy, comparable to expensive commercial agents. New cost‐effective avenues to develop metal–organic‐framework‐based nonviral vectors for efficient gene delivery and expression are provided.

Modulating the Biofunctionality of Metal–Organic‐Framework‐Encapsulated Enzymes through Controllable Embedding Patterns

“…[10,11,56,57] Furthermore,i ncreasing efforts were devoted to construct biomacromolecule@nanoZIF-8 intracellular delivery systems for protein-and gene-based theranostics. [25,[58][59][60] These applications receive more and more attention because of the high loading efficiency and protecting effect of ZIF-8, and the convenient de novo synthesis process.H erein, we highlighted the importance of the embedding patterns for facilitating and preserving the biofunctionality of abiomacromolecule encapsulated within ZIF-8. Importantly,o ur work demonstrated that the embedding patterns can be controlled by chemical modification of the amino acids of the protein that enabled the modulation of the biofunctionality of proteins@ZIF-8.…”

Modulating the Biofunctionality of Metal–Organic‐Framework‐Encapsulated Enzymes through Controllable Embedding Patterns

“…Many biomacromolecules@ZIF‐8, including enzymes@ZIF‐8, were recently developed as robust platform for biocatalysis, biosensing, biobanking and bioprocessing . Furthermore, increasing efforts were devoted to construct biomacromolecule@nanoZIF‐8 intracellular delivery systems for protein‐ and gene‐based theranostics . These applications receive more and more attention because of the high loading efficiency and protecting effect of ZIF‐8, and the convenient de novo synthesis process.…”

Accurate cancer cell identification and microRNA silencing induced therapy using tailored DNA tetrahedron nanostructures

“…Gene silencing as a kind of gene therapy has now been considered as one of the most promising options to overcome the limitations of traditional cancer therapy. [19][20][21] It can induce sequence-specic inhibition of oncogene expression or translation through the delivery of antagomirs to cancer cells, which makes it possess advantages of high specicity, improved safety, high efficacy and unrestricted choice of targets. 22,23 For example, leucine-rich repeat-containing G protein-coupled receptor 5 (Lgr5) is a novel gastric cancer marker, and silencing its expression with antagomirs could efficiently inhibit cancer angiogenesis.…”