Controlled Monofunctionalization of Molecular Spherical Nucleic Acids on a Buckminster Fullerene Core

Overview

Journal Bioconjug Chem

Publisher American Chemical Society

Specialty Biochemistry

Date 2021 May 17

PMID 33998229

Citations 8

Authors

Vijay Gulumkar

Antti Aarela

Olli Moisio

Jani Rahkila

Ville Tahtinen

Laura Leimu

Niko Korsoff

Heidi Korhonen

Paivi Poijarvi-Virta

Satu Mikkola

Victor Nesati

Elina Vuorimaa-Laukkanen

Tapani Viitala

Marjo Yliperttula

Anne Roivainen

Pasi Virta

Affiliations

Soon will be listed here.

Abstract

An azide-functionalized 12-armed Buckminster fullerene has been monosubstituted in organic media with a substoichiometric amount of cyclooctyne-modified oligonucleotides. Exposing the intermediate products then to the same reaction (i.e., strain-promoted alkyne-azide cycloaddition, SPAAC) with an excess of slightly different oligonucleotide constituents in an aqueous medium yields molecularly defined monofunctionalized spherical nucleic acids (SNAs). This procedure offers a controlled synthesis scheme in which one oligonucleotide arm can be functionalized with labels or other conjugate groups (1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid, DOTA, and Alexa-488 demonstrated), whereas the rest of the 11 arms can be left unmodified or modified by other conjugate groups in order to decorate the SNAs' outer sphere. Extra attention has been paid to the homogeneity and authenticity of the C-azide scaffold used for the assembly of full-armed SNAs.

Citing Articles

Biological Evaluation of Molecular Spherical Nucleic Acids: Targeting Tumors via a Hybridization-Based Folate Decoration.

Auchynnikava T, Aarela A, Moisio O, Liljenback H, Andriana P, Iqbal I ACS Omega. 2025; 10(6):6003-6014.

PMID: 39989783 PMC: 11840764. DOI: 10.1021/acsomega.4c10047.

Click Chemistry as an Efficient Toolbox for Coupling Sterically Hindered Molecular Systems to Obtain Advanced Materials for Nanomedicine.

Cabrera-Quinones N, Lopez-Mendez L, Cruz-Hernandez C, Guadarrama P Int J Mol Sci. 2025; 26(1.

PMID: 39795895 PMC: 11719597. DOI: 10.3390/ijms26010036.

Recent advances in gene delivery nanoplatforms based on spherical nucleic acids.

Valatabar N, Oroojalian F, Kazemzadeh M, Mokhtarzadeh A, Safaralizadeh R, Sahebkar A J Nanobiotechnology. 2024; 22(1):386.

PMID: 38951806 PMC: 11218236. DOI: 10.1186/s12951-024-02648-5.

Tetrazine Glycoconjugate for Pretargeted Positron Emission Tomography Imaging of -Cyclooctene-Functionalized Molecular Spherical Nucleic Acids.

Auchynnikava T, Aarela A, Liljenback H, Jarvinen J, Andriana P, Kovacs L ACS Omega. 2023; 8(48):45326-45336.

PMID: 38075748 PMC: 10702189. DOI: 10.1021/acsomega.3c04041.

Making the Next Generation of Therapeutics: mRNA Meets Synthetic Biology.

Hincer A, Ahan R, Aras E, Safak Seker U ACS Synth Biol. 2023; 12(9):2505-2515.

PMID: 37672348 PMC: 10510722. DOI: 10.1021/acssynbio.3c00253.

References

Chinen A, Guan C, Ko C, Mirkin C . The Impact of Protein Corona Formation on the Macrophage Cellular Uptake and Biodistribution of Spherical Nucleic Acids. Small. 2017; 13(16). PMC: 5493144. DOI: 10.1002/smll.201603847. View

Zhang K, Hao L, Hurst S, Mirkin C . Antibody-linked spherical nucleic acids for cellular targeting. J Am Chem Soc. 2012; 134(40):16488-91. PMC: 3501255. DOI: 10.1021/ja306854d. View

Jensen S, Day E, Ko C, Hurley L, Luciano J, Kouri F . Spherical nucleic acid nanoparticle conjugates as an RNAi-based therapy for glioblastoma. Sci Transl Med. 2013; 5(209):209ra152. PMC: 4017940. DOI: 10.1126/scitranslmed.3006839. View

Zheng D, Giljohann D, Chen D, Massich M, Wang X, Iordanov H . Topical delivery of siRNA-based spherical nucleic acid nanoparticle conjugates for gene regulation. Proc Natl Acad Sci U S A. 2012; 109(30):11975-80. PMC: 3409786. DOI: 10.1073/pnas.1118425109. View

Keinanen O, Fung K, Pourat J, Jallinoja V, Vivier D, Pillarsetty N . Pretargeting of internalizing trastuzumab and cetuximab with a F-tetrazine tracer in xenograft models. EJNMMI Res. 2017; 7(1):95. PMC: 5712296. DOI: 10.1186/s13550-017-0344-6. View

Astakhova I, Kumar T, Campbell M, Ustinov A, Korshun V, Wengel J . Branched DNA nanostructures efficiently stabilised and monitored by novel pyrene-perylene 2'-α-L-amino-LNA FRET pairs. Chem Commun (Camb). 2012; 49(5):511-3. DOI: 10.1039/c2cc37547h. View

Krishnamoorthy K, Hoffmann K, Kewalramani S, Brodin J, Moreau L, Mirkin C . Defining the Structure of a Protein-Spherical Nucleic Acid Conjugate and Its Counterionic Cloud. ACS Cent Sci. 2018; 4(3):378-386. PMC: 5879473. DOI: 10.1021/acscentsci.7b00577. View

Patel P, Giljohann D, Daniel W, Zheng D, Prigodich A, Mirkin C . Scavenger receptors mediate cellular uptake of polyvalent oligonucleotide-functionalized gold nanoparticles. Bioconjug Chem. 2010; 21(12):2250-6. PMC: 3241523. DOI: 10.1021/bc1002423. View

An F, Gong B, Wang H, Yu D, Zhao G, Lin L . miR-15b and miR-16 regulate TNF mediated hepatocyte apoptosis via BCL2 in acute liver failure. Apoptosis. 2012; 17(7):702-16. DOI: 10.1007/s10495-012-0704-7. View

10.

Li H, Zhang B, Lu X, Tan X, Jia F, Xiao Y . Molecular spherical nucleic acids. Proc Natl Acad Sci U S A. 2018; 115(17):4340-4344. PMC: 5924931. DOI: 10.1073/pnas.1801836115. View

11.

Rosi N, Giljohann D, Thaxton C, Lytton-Jean A, Han M, Mirkin C . Oligonucleotide-modified gold nanoparticles for intracellular gene regulation. Science. 2006; 312(5776):1027-30. DOI: 10.1126/science.1125559. View

12.

Jadhav S, Kakela M, Makila J, Kiugel M, Liljenback H, Virta J . Synthesis and In Vivo PET Imaging of Hyaluronan Conjugates of Oligonucleotides. Bioconjug Chem. 2015; 27(2):391-403. DOI: 10.1021/acs.bioconjchem.5b00477. View

13.

Chinen A, Ferrer J, Merkel T, Mirkin C . Relationships between Poly(ethylene glycol) Modifications on RNA-Spherical Nucleic Acid Conjugates and Cellular Uptake and Circulation Time. Bioconjug Chem. 2016; 27(11):2715-2721. PMC: 5439959. DOI: 10.1021/acs.bioconjchem.6b00483. View

14.

Yan W, Seifermann S, Pierrat P, Brase S . Synthesis of highly functionalized C60 fullerene derivatives and their applications in material and life sciences. Org Biomol Chem. 2014; 13(1):25-54. DOI: 10.1039/c4ob01663g. View

15.

Makila J, Kiviniemi A, Saanijoki T, Liljenback H, Kakela M, Jadhav S . Noninvasive and Quantitative Monitoring of the Distributions and Kinetics of MicroRNA-Targeting Molecules in Vivo by Positron Emission Tomography. Mol Pharm. 2019; 16(4):1507-1515. PMC: 6727608. DOI: 10.1021/acs.molpharmaceut.8b01169. View

16.

Nierengarten I, Nierengarten J . Fullerene sugar balls: a new class of biologically active fullerene derivatives. Chem Asian J. 2014; 9(6):1436-44. DOI: 10.1002/asia.201400133. View

17.

Wu X, Choi C, Zhang C, Hao L, Mirkin C . Intracellular fate of spherical nucleic acid nanoparticle conjugates. J Am Chem Soc. 2014; 136(21):7726-33. PMC: 4046773. DOI: 10.1021/ja503010a. View

18.

Narayan S, Choi C, Hao L, Calabrese C, Auyeung E, Zhang C . The Sequence-Specific Cellular Uptake of Spherical Nucleic Acid Nanoparticle Conjugates. Small. 2015; 11(33):4173-82. PMC: 4560454. DOI: 10.1002/smll.201500027. View

19.

Alhasan A, Patel P, Choi C, Mirkin C . Exosome encased spherical nucleic acid gold nanoparticle conjugates as potent microRNA regulation agents. Small. 2013; 10(1):186-92. PMC: 3947239. DOI: 10.1002/smll.201302143. View

20.

Fong L, Wang Z, Schatz G, Luijten E, Mirkin C . The Role of Structural Enthalpy in Spherical Nucleic Acid Hybridization. J Am Chem Soc. 2018; 140(20):6226-6230. PMC: 6001361. DOI: 10.1021/jacs.8b03459. View