Lipid-Based Nanocarriers in Renal RNA Therapy

Abstract

Kidney disease is a multifactorial problem, with a growing prevalence and an increasing global burden. With the latest worldwide data suggesting that chronic kidney disease (CKD) is the 12th leading cause of death, it is no surprise that CKD remains a public health problem that requires urgent attention. Multiple factors contribute to kidney disease, each with its own pathophysiology and pathogenesis. Furthermore, microRNAs (miRNAs) have been linked to several types of kidney diseases. As dysregulation of miRNAs is often seen in some diseases, there is potential in the exploitation of this for therapeutic applications. In addition, uptake of interference RNA has been shown to be rapid in kidneys making them a good candidate for RNA therapy. The latest advancements in RNA therapy and lipid-based nanocarriers have enhanced the effectiveness and efficiency of RNA-related drugs, thereby making RNA therapy a viable treatment option for renal disease. This is especially useful for renal diseases, for which a suitable treatment is not yet available. Moreover, the high adaptability of RNA therapy combined with the low risk of lipid-based nanocarriers make for an attractive treatment choice. Currently, there are only a small number of RNA-based drugs related to renal parenchymal disease, most of which are in different stages of clinical trials. We propose the use of miRNAs or short interfering RNAs coupled with a lipid-based nanocarrier as a delivery vehicle for managing renal disease.

Nanoparticle drug delivery systems for synergistic delivery of tumor therapy

“…Lipid-based nanocarriers were shown to be among the most successful approach for drug and gene delivery ( Ansari et al, 2020 ). It can modify the physicochemical properties by connecting with different materials to improve co-delivery efficiency ( Buya et al, 2021 ; Su et al, 2022 ).…”

Non-coding RNAs as potential biomarkers and therapeutic targets in polycystic kidney disease

“…1) exosomes derived from various cell types, like mesenchymal stem cells, have the potential to be drug carriers for ncRNAs or oligonucleotides due to their stability, minimal immune response, and editable surface with various RNAs loading strategies including diffusion via a concentration gradient, transfection, or physical treatments like electroporation, which can also expand the cargo loading capability of exosomes ( Jin et al, 2021 ). 2) Nanoparticles, which refer to a stable structure with a protective layer that can encapsulate and protect inner agents, and be modified with ligands or antibodies on their surface for kidney-specific targeting at a nano scale, have the potential to improve the pharmacokinetics, biodistribution, toxicity, and efficacy of encapsulated drugs: 1) inorganic system like pSi and magnetic particles ( Tsai et al, 2019 ); 2) polymeric system including synthetic polymerics like polymeric CXCR4 inhibitors ( Tang et al, 2022 ) and natural polymers such as chitosan ( Chen et al, 2019 ); 3) lipid-based system ( Su et al, 2022 ); 4) carbon-nanotubes ( Alidori et al, 2016 ). LNA = locked nucleic acid; CPP = cell penetrating peptide; GalNAc = N-acetylgalactosamine; pHLIP = pH (low) insertion peptides.…”

Recent advancements in design of nucleic acid nanocarriers for controlled drug delivery

“…38,39 The first known usage of organic particles for encapsulating DNA was seen in the early 80's, 40 while usage of DNA self-assembly on inorganic nanoparticles was developed in the late 90's. 41 Further evolution of these structures has led to numerous clinical trials that focus on applying nucleic acid nanostructures to nanomedicine including lipid nanoparticles carrying mRNA for cancer developed by Moderna and BioNTech, 42 lipid-based carriers of RNA for renal diseases, 43 and PEG-Bioconjugates carrying siRNA for infectious diseases. 44 In this review, a summary of the physical properties of nanocarriers and their effect on in vivo fate will be discussed.…”