TY - JOUR
T1 - Assembly of Bleomycin Saccharide-Decorated Spherical Nucleic Acids
AU - Tähtinen, Ville
AU - Gulumkar, Vijay
AU - Maity, Sajal K.
AU - Yliperttula, Ann Mari
AU - Siekkinen, Saara
AU - Laine, Toni
AU - Lisitsyna, Ekaterina
AU - Haapalehto, Iida
AU - Viitala, Tapani
AU - Vuorimaa-Laukkanen, Elina
AU - Yliperttula, Marjo
AU - Virta, Pasi
N1 - Funding Information:
P.V. acknowledges the Academy of Finland project (308931) and Business Finland Ecosystem project (448/31/2018). M.Y. acknowledges Academy of Finland’s Flagship Programme under Project No. 337430 (Gene, Cell and Nano Therapy Competence Cluster for the Treatment of Chronic Diseases, GeneCellNano).
Funding Information:
Imaging was performed at the Cell Imaging and Cytometry Core, Turku Bioscience Centre, Turku, Finland, with the support of Biocenter Finland. P.V. acknowledges the Academy of Finland project (308931) and Business Finland Ecosystem project (448/31/2018). M.Y. acknowledges Academy of Finland?s Flagship Programme under Project No. 337430 (Gene, Cell and Nano Therapy Competence Cluster for the Treatment of Chronic Diseases, GeneCellNano).
Publisher Copyright:
© 2022 The Authors. Published by American Chemical Society
PY - 2022/1/19
Y1 - 2022/1/19
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=85122790062&partnerID=8YFLogxK
U2 - 10.1021/acs.bioconjchem.1c00539
DO - 10.1021/acs.bioconjchem.1c00539
M3 - Article
C2 - 34985282
AN - SCOPUS:85122790062
SN - 1043-1802
VL - 33
SP - 206
EP - 218
JO - Bioconjugate Chemistry
JF - Bioconjugate Chemistry
IS - 1
ER -