Journal
BIOCONJUGATE CHEMISTRY
Volume 33, Issue 1, Pages 206-218Publisher
AMER CHEMICAL SOC
DOI: 10.1021/acs.bioconjchem.1c00539
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Funding
- Academy of Finland [308931]
- Business Finland Ecosystem project [448/31/2018]
- Academy of Finland's Flagship Programme [337430]
- Academy of Finland (AKA) [337430] Funding Source: Academy of Finland (AKA)
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Glyco-decorated spherical nucleic acids (SNAs) are attractive delivery vehicles that can hide the unfavorable distribution properties of loaded oligonucleotides. In this study, glyco-AONARV7 conjugates were successfully synthesized and used to form glyco-decorated SNAs. Cellular uptake experiments demonstrated that these glyco-decorated SNAs efficiently entered prostate cancer cells and showed marked variation in intracellular distribution.
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 glycodecorated 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.
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