Biological Evaluation of Molecular Spherical Nucleic Acids: Targeting Tumors Via a Hybridization-Based Folate Decoration

Overview

Journal ACS Omega

Publisher American Chemical Society

Specialty Chemistry

Date 2025 Feb 24

PMID 39989783

Authors

Tatsiana Auchynnikava

Antti Aarela

Olli Moisio

Heidi Liljenback

Putri Andriana

Imran Iqbal

Toni Laine

Senthil Palani

Jyrki Lehtimaki

Johan Rajander

Harri Salo

Anu J Airaksinen

Pasi Virta

Anne Roivainen

Affiliations

Soon will be listed here.

Abstract

Folate receptors (FRs), membrane-bound proteins that bind specifically to folate with high affinity, are overexpressed by various cancer types and are therefore used as targets for delivery of therapeutic agents. Molecular spherical nucleic acids (MSNAs) are dendritic formulations of oligonucleotides (ONs) that may have advantages over linear parent ONs with respect to delivery properties. Here, we assembled folate-decorated MSNAs, site-specifically radiolabeled them, and then biologically evaluated their effects in mice bearing HCC1954 breast cancer xenograft tumors. The biodistribution of intravenously administered F-radiolabeled MSNAs was monitored using positron emission tomography/computed tomography imaging. The results revealed higher accumulation of folate-decorated MSNAs in FR-expressing organs such as the liver, kidney, and spleen, as well as a higher tumor-to-muscle ratio than that observed for MSNAs without the folate decoration. However, the observed increase was statistically significant only for MSNA structures with a PO backbone. The observed selective uptake of folate-decorated MSNAs highlights their potential as targeted delivery vehicles for therapeutic and diagnostic agents in FR-overexpressing cancers.

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