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<p>Oligonucleotide-carbohydrate conjugates is an efficient strategy to provide cell-specific delivery of oligonucleotides. Combining the multivalent nature of molecular spherical nucleic acids (MSNAs) with a proper glyco-decoration results in multiglyco-oligonucleotide constructs, which could potentially increase the sugar-based cell surface recognition and widen the scope of sugars applied for delivery. On the other hand, MSNAs are prone to scavenger A-receptor-mediated endocytosis, the strength of which can hardly be compensated by the sugar-mediated delivery. In this report, the formation of bleomycin saccharide-decorated MSNAs was evaluated by steady-state and time-resolved spectroscopies, revealing significant effects on the fluorescence quantum yields and negative cooperativity. Cellular uptake of the MSNAs in cancerous 22Rv1 and PC3 cell-lines was evaluated by fluorescence-lifetime imaging microscopy (FLIM), wide-field microscopy, and flow cytometry. In addition, optimized synthesis and further characterization (homogeneity and molecular mass evaluation, DNase I stability) of these hybridization-mediated macromolecular glycoclusters, consisting of 36 mono/disaccharide units, were described.</p>

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Formation and cellular uptake of Bleomycin saccharide decorated molecular spherical nucleic acids evaluated by time-resolved fluorescence spectroscopy

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2026年5月12日

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  • Toni Laine,
  • Iida Kähärä,
  • Ann-Mari Yliperttula,
  • Ezgi Özliseli,
  • Saara Siekkinen,
  • Emilia Löfman,
  • Ekaterina Lisitsyna,
  • Annika Gerlander,
  • Vijay Gulumkar,
  • Elina Vuorimaa-Laukkanen,
  • Jessica M. Rosenholm,
  • Marjo Yliperttula,
  • Päivi Poijärvi-Virta,
  • Pasi Virta

摘要

Oligonucleotide-carbohydrate conjugates is an efficient strategy to provide cell-specific delivery of oligonucleotides. Combining the multivalent nature of molecular spherical nucleic acids (MSNAs) with a proper glyco-decoration results in multiglyco-oligonucleotide constructs, which could potentially increase the sugar-based cell surface recognition and widen the scope of sugars applied for delivery. On the other hand, MSNAs are prone to scavenger A-receptor-mediated endocytosis, the strength of which can hardly be compensated by the sugar-mediated delivery. In this report, the formation of bleomycin saccharide-decorated MSNAs was evaluated by steady-state and time-resolved spectroscopies, revealing significant effects on the fluorescence quantum yields and negative cooperativity. Cellular uptake of the MSNAs in cancerous 22Rv1 and PC3 cell-lines was evaluated by fluorescence-lifetime imaging microscopy (FLIM), wide-field microscopy, and flow cytometry. In addition, optimized synthesis and further characterization (homogeneity and molecular mass evaluation, DNase I stability) of these hybridization-mediated macromolecular glycoclusters, consisting of 36 mono/disaccharide units, were described.