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Development of Focused Ultrasound-Assisted Nanoplexes for RNA Delivery

Publiceringsår

2024

Upphovspersoner

Ranjan, Sanjeev; Bosch, Stef; Lukkari, Hannamari; Schirmer, Johanna; Aaltonen, Niina; Nieminen, Heikki J.; Lehto, Vesa-Pekka; Urtti, Arto; Lajunen, Tatu; Rilla, Kirsi

Abstrakt

RNA-based therapeutics, including siRNA, have obtained recognition in recent years due to their potential to treat various chronic and rare diseases. However, there are still limitations to lipid-based drug delivery systems in the clinical use of RNA therapeutics due to the need for optimization in the design and the preparation process. In this study, we propose adaptive focused ultrasound (AFU) as a drug loading technique to protect RNA from degradation by encapsulating small RNA in nanoliposomes, which we term nanoplexes. The AFU method is non-invasive and isothermal, as nanoplexes are produced without direct contact with any external materials while maintaining precise temperature control according to the desired settings. The controllability of sample treatments can be effectively modulated, allowing for a wide range of ultrasound intensities to be applied. Importantly, the absence of co-solvents in the process eliminates the need for additional substances, thereby minimizing the potential for cross-contaminations. Since AFU is a non-invasive method, the entire process can be conducted under sterile conditions. A minimal volume (300 μL) is required for this process, and the treatment is speedy (10 min in this study). Our in vitro experiments with silencer CD44 siRNA, which performs as a model therapeutic drug in different mammalian cell lines, showed encouraging results (knockdown > 80%). To quantify gene silencing efficacy, we employed quantitative polymerase chain reaction (qPCR). Additionally, cryo-electron microscopy (cryo-EM) and atomic force microscopy (AFM) techniques were employed to capture images of nanoplexes. These images revealed the presence of individual nanoparticles measuring approximately 100–200 nm in contrast with the random distribution of clustered complexes observed in ultrasound-untreated samples of liposome nanoparticles and siRNA. AFU holds great potential as a standardized liposome processing and loading method because its process is fast, sterile, and does not require additional solvents.
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Organisationer och upphovspersoner

Aalto-universitetet

Nieminen Heikki Orcid -palvelun logo

Ranjan Sanjeev Orcid -palvelun logo

Östra Finlands universitet

Lehto Vesa-Pekka

Lajunen Tatu Eero Anton Orcid -palvelun logo

Rilla Kirsi Johanna

Aaltonen Niina Orvokki

Ranjan Sanjeev

Bosch Stef Daisy L.

Jyväskylä universitet

Schirmer Johanna Orcid -palvelun logo

Helsingfors universitet

Urtti Arto

Nieminen Heikki J.

Lajunen Tatu

Publikationstyp

Publikationsform

Artikel

Moderpublikationens typ

Tidning

Artikelstyp

En originalartikel

Målgrupp

Vetenskaplig

Kollegialt utvärderad

Kollegialt utvärderad

UKM:s publikationstyp

A1 Originalartikel i en vetenskaplig tidskrift

Publikationskanalens uppgifter

Moderpublikationens namn

Nanomaterials

Volym

14

Nummer

13

Artikelnummer

1089

Publikationsforum

82604

Publikationsforumsnivå

1

Öppen tillgång

Öppen tillgänglighet i förläggarens tjänst

Ja

Öppen tillgång till publikationskanalen

Helt öppen publikationskanal

Parallellsparad

Ja

Övriga uppgifter

Vetenskapsområden

Kemi; Nanoteknologi; Farmaci; Biomedicinska vetenskaper

Nyckelord

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Förlagets internationalitet

Internationell

Språk

engelska

Internationell sampublikation

Nej

Sampublikation med ett företag

Ja

DOI

10.3390/nano14131089

Publikationen ingår i undervisnings- och kulturministeriets datainsamling

Ja