Vault, viral, and virus-like nanoparticles for targeted cancer therapy

Iravani, Siavash; Varma, Rajender S.

doi:10.1039/d3ma00171g

Cited by 1 publication

(1 citation statement)

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“…Regardless of its biological roles, the vault NP, as produced by assembly of the sole MVP, has been exploited as a biotechnological tool suitable for several applications. Mostly (but not exclusively), it has been used as a nano-vector for drug delivery to cancer cells [ 10 , 21 , 38 ], although other applications have also been recently developed, notably laccase immobilization for decolorization and detoxification of synthetic dye compounds [ 39 ].…”

Section: Discussionmentioning

confidence: 99%

An Efficient Method for Vault Nanoparticle Conjugation with Finely Adjustable Amounts of Antibodies and Small Molecules

Tomaino,

Pantaleoni,

D’Urzo

et al. 2024

IJMS

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Vaults are eukaryotic ribonucleoproteins consisting of 78 copies of the major vault protein (MVP), which assemble into a nanoparticle with an about 60 nm volume-based size, enclosing other proteins and RNAs. Regardless of their physiological role(s), vaults represent ideal, natural hollow nanoparticles, which are produced by the assembly of the sole MVP. Here, we have expressed in Komagataella phaffi and purified an MVP variant carrying a C-terminal Z peptide (vault-Z), which can tightly bind an antibody’s Fc portion, in view of targeted delivery. Via surface plasmon resonance analysis, we could determine a 2.5 nM affinity to the monoclonal antibody Trastuzumab (Tz)/vault-Z 1:1 interaction. Then, we characterized the in-solution interaction via co-incubation, ultracentrifugation, and analysis of the pelleted proteins. This showed virtually irreversible binding up to an at least 10:1 Tz/vault-Z ratio. As a proof of concept, we labeled the Fc portion of Tz with a fluorophore and conjugated it with the nanoparticle, along with either Tz or Cetuximab, another monoclonal antibody. Thus, we could demonstrate antibody-dependent, selective uptake by the SKBR3 and MDA-MB 231 breast cancer cell lines. These investigations provide a novel, flexible technological platform that significantly extends vault-Z’s applications, in that it can be stably conjugated with finely adjusted amounts of antibodies as well as of other molecules, such as fluorophores, cell-targeting peptides, or drugs, using the Fc portion as a scaffold.

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