Assembly of Bleomycin Saccharide-Decorated Spherical Nucleic Acids

Ville Tähtinen, Vijay Gulumkar, Sajal K. Maity, Ann Mari Yliperttula, Saara Siekkinen, Toni Laine, Ekaterina Lisitsyna, Iida Haapalehto, Tapani Viitala, Elina Vuorimaa-Laukkanen, Marjo Yliperttula, Pasi Virta

Tutkimustuotos: ArtikkeliScientificvertaisarvioitu

Abstrakti

Glyco-decorated spherical nucleic acids (SNAs) may be attractive delivery vehicles, emphasizing the sugar-specific effect on the outer sphere of the construct and at the same time hiding unfavorable distribution properties of the loaded oligonucleotides. As examples of such nanoparticles, tripodal sugar constituents of bleomycin were synthesized and conjugated with a fluorescence-labeled antisense oligonucleotide (AONARV7). Successive copper(I)-catalyzed azide-alkyne and strain-promoted alkyne-nitrone cycloadditions (SPANC) were utilized for the synthesis. Then, the glyco-AONARV7 conjugates were hybridized with complementary strands of a C60-based molecular spherical nucleic acid (i.e., a hybridization-mediated carrier). The formation and stability of these assembled glyco-decorated SNAs were evaluated by polyacrylamide gel electrophoresis (PAGE), UV melting profile analysis, and time-resolved fluorescence spectroscopy. Association constants were extracted from time-resolved fluorescence data. Preliminary cellular uptake experiments of the glyco-AONARV7 conjugates (120 nM solutions) and of the corresponding glyco-decorated SNAs (10 nM solutions) with human prostate cancer cells (PC3) showed an efficient uptake in each case. A marked variation in intracellular distribution was observed.

AlkuperäiskieliEnglanti
Sivut206–218
JulkaisuBioconjugate Chemistry
Vuosikerta33
Numero1
DOI - pysyväislinkit
TilaJulkaistu - 2022
OKM-julkaisutyyppiA1 Alkuperäisartikkeli tieteellisessä aikakauslehdessä

!!ASJC Scopus subject areas

  • Biotechnology
  • Bioengineering
  • Biomedical Engineering
  • Pharmacology
  • Pharmaceutical Science
  • Organic Chemistry

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