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Assembly of Bleomycin Saccharide-Decorated Spherical Nucleic Acids
Ville Tähtinen1, Vijay Gulumkar1, Sajal K Maity1
1Department of Chemistry, University of Turku, FI-20500 Turku, Finland.
Bioconjugate Chemistry
|January 5, 2022
Summary
Glyco-decorated spherical nucleic acids (SNAs) show promise as delivery vehicles. These novel nanoparticles efficiently entered prostate cancer cells, with varied intracellular distribution observed.
Area of Science:
- Biotechnology
- Nanomedicine
- Chemical Biology
Background:
- Spherical nucleic acids (SNAs) are promising nanocarriers.
- Glycosylation can enhance nanoparticle properties.
- Antisense oligonucleotides (AONs) are used in gene therapy.
Purpose of the Study:
- To synthesize and characterize novel glyco-decorated SNAs.
- To evaluate their potential as delivery vehicles for AONs.
- To investigate cellular uptake and intracellular distribution.
Main Methods:
- Synthesis of tripodal sugar constituents and conjugation with AONARV7 using click chemistry (copper(I)-catalyzed azide-alkyne cycloaddition and strain-promoted alkyne-nitrone cycloaddition).
- Hybridization of glyco-AONARV7 conjugates with C60-based molecular SNAs.
- Characterization of SNA formation and stability using PAGE, UV melting, and time-resolved fluorescence spectroscopy.
- Cellular uptake studies in human prostate cancer cells (PC3).
Main Results:
- Successful synthesis and assembly of glyco-decorated SNAs.
- Demonstrated stability and hybridization of the SNAs.
- Efficient cellular uptake of both glyco-AONARV7 conjugates and glyco-SNAs in PC3 cells.
- Observed variations in intracellular distribution.
Conclusions:
- Glyco-decorated SNAs are effective carriers for AONs.
- These nanostructures exhibit efficient cellular uptake in cancer cells.
- Further investigation into intracellular trafficking is warranted.
