The Vault Nanoparticle: A Gigantic Ribonucleoprotein Assembly Involved in Diverse Physiological and Pathological Phenomena and an Ideal Nanovector for Drug Delivery and Therapy

Abstract

The vault nanoparticle is a eukaryotic ribonucleoprotein complex consisting of 78 individual 97 kDa-“major vault protein” (MVP) molecules that form two symmetrical, cup-shaped, hollow halves. It has a huge size (72.5 × 41 × 41 nm) and an internal cavity, wherein the vault poly(ADP-ribose) polymerase (vPARP), telomerase-associated protein-1 (TEP1), and some small untranslated RNAs are accommodated. Plenty of literature reports on the biological role(s) of this nanocomplex, as well as its involvement in diseases, mostly oncological ones. Nevertheless, much has still to be understood as to how vault participates in normal and pathological mechanisms. In this comprehensive review, current understanding of its biological roles is discussed. By different mechanisms, vault’s individual components are involved in major cellular phenomena, which result in protection against cellular stresses, such as DNA-damaging agents, irradiation, hypoxia, hyperosmotic, and oxidative conditions. These diverse cellular functions are accomplished by different mechanisms, mainly gene expression reprogramming, activation of proliferative/prosurvival signaling pathways, export from the nucleus of DNA-damaging drugs, and import of specific proteins. The cellular functions of this nanocomplex may also result in the onset of pathological conditions, mainly (but not exclusively) tumor proliferation and multidrug resistance. The current understanding of its biological roles in physiological and pathological processes should also provide new hints to extend the scope of its exploitation as a nanocarrier for drug delivery.

Small but Powerful: The Human Vault RNAs as Multifaceted Modulators of Pro-Survival Characteristics and Tumorigenesis

“…There are also a few studies connecting the vault complex to drug resistance [ 28 , 51 , 115 , 116 , 117 , 118 , 119 , 120 , 121 , 122 ], although it is still under dispute since reliable changes of drug resistance were not observed in in vivo experiments using MVP KO mice [ 26 , 123 , 124 ]. In addition to nuclear-cytoplasmic transport and drug resistance, it was reported that the vault complex participates in intracellular signaling pathways, DNA damage repair and anti-apoptotic processes, most of which are closely related to cancer [ 50 , 125 , 126 , 127 , 128 , 129 ].…”

Role of Fasciola hepatica Small RNAs in the Interaction With the Mammalian Host

“…Vault ribonucleoproteins are large hollow barrel-like shape particles in the cytoplasm of many eukaryotic cells. Although little is known yet on their function, they have been involved in key regulatory roles including autophagy, apoptosis and modulation of gene expression [reviewed by Frascotti et al, (2021)]. Even more, recent evidence has shown that human vtRNA1-1 could guide sequence-specific cleavage of a complementary target RNA (Frascotti et al, 2021).…”

Biomaterials, biological molecules, and polymers in developing vaccines

“…Vault particles, large, hollow ribonucleoprotein cages, have been investigated as drug delivery vehicles. Their roles in several mechanisms and pathways have been studied and they are emerging as potential delivery vehicles for therapeutic molecules [83][84][85][86]. However, they have not been widely studied for vaccine development.…”