Abstract
We describe a new, and vastly superior approach for labeling spherical nucleic acid conjugates (SNAs) with diagnostic probes. SNAs have been shown to provide the unique ability to traverse the cell membrane and deliver surface conjugated DNA into cells while preserving the DNA from nuclease degradation. Our previous work on preparing diagnostically labeled SNAs was labor intensive, relatively low yielding, and costly. Here, we describe a straightforward and facile preparation for labeling SNAs with optical and MR imaging probes with significantly improved physical properties. The synthesis of Gd(III) labeled DNA Au nanoparticle conjugates is achieved by sequential conjugation of 3′-thiol-modified oligonucleotides and cofunctionalization of the particle surface with the subsequent addition of 1,2 diothiolate modified chelates of Gd(III) (abbreviated: DNA-GdIII@AuNP). This new generation of SNA conjugates has a 2-fold increase of DNA labeling and a 1.4-fold increase in Gd(III) loading compared to published constructs. Furthermore, the relaxivity (r1) is observed to increase 4.5-fold compared to the molecular dithiolane-Gd(III) complex, and 1.4-fold increase relative to previous particle constructs where the Gd(III) complexes were conjugated to the oligonucleotides rather than directly to the Au particle. Importantly, this simplified approach (2 steps) exploits the advantages of previous Gd(III) labeled SNA platforms; however, this new approach is scalable and eliminates modification of DNA for attaching the contrast agent, and the particles exhibit improved cell labeling.
| Original language | English (US) |
|---|---|
| Pages (from-to) | 3544-3549 |
| Number of pages | 6 |
| Journal | Bioconjugate Chemistry |
| Volume | 29 |
| Issue number | 11 |
| DOIs | |
| State | Published - Nov 21 2018 |
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ASJC Scopus subject areas
- Biotechnology
- Bioengineering
- Biomedical Engineering
- Pharmacology
- Pharmaceutical Science
- Organic Chemistry
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A Markedly Improved Synthetic Approach for the Preparation of Multifunctional Au-DNA Nanoparticle Conjugates Modified with Optical and MR Imaging Probes. / Rotz, Matthew W.; Holbrook, Robert J.; Macrenaris, Keith W.; Meade, Thomas J.
In: Bioconjugate Chemistry, Vol. 29, No. 11, 21.11.2018, p. 3544-3549.Research output: Contribution to journal › Article
TY - JOUR
T1 - A Markedly Improved Synthetic Approach for the Preparation of Multifunctional Au-DNA Nanoparticle Conjugates Modified with Optical and MR Imaging Probes
AU - Rotz, Matthew W.
AU - Holbrook, Robert J.
AU - Macrenaris, Keith W.
AU - Meade, Thomas J.
PY - 2018/11/21
Y1 - 2018/11/21
N2 - We describe a new, and vastly superior approach for labeling spherical nucleic acid conjugates (SNAs) with diagnostic probes. SNAs have been shown to provide the unique ability to traverse the cell membrane and deliver surface conjugated DNA into cells while preserving the DNA from nuclease degradation. Our previous work on preparing diagnostically labeled SNAs was labor intensive, relatively low yielding, and costly. Here, we describe a straightforward and facile preparation for labeling SNAs with optical and MR imaging probes with significantly improved physical properties. The synthesis of Gd(III) labeled DNA Au nanoparticle conjugates is achieved by sequential conjugation of 3′-thiol-modified oligonucleotides and cofunctionalization of the particle surface with the subsequent addition of 1,2 diothiolate modified chelates of Gd(III) (abbreviated: DNA-GdIII@AuNP). This new generation of SNA conjugates has a 2-fold increase of DNA labeling and a 1.4-fold increase in Gd(III) loading compared to published constructs. Furthermore, the relaxivity (r1) is observed to increase 4.5-fold compared to the molecular dithiolane-Gd(III) complex, and 1.4-fold increase relative to previous particle constructs where the Gd(III) complexes were conjugated to the oligonucleotides rather than directly to the Au particle. Importantly, this simplified approach (2 steps) exploits the advantages of previous Gd(III) labeled SNA platforms; however, this new approach is scalable and eliminates modification of DNA for attaching the contrast agent, and the particles exhibit improved cell labeling.
AB - We describe a new, and vastly superior approach for labeling spherical nucleic acid conjugates (SNAs) with diagnostic probes. SNAs have been shown to provide the unique ability to traverse the cell membrane and deliver surface conjugated DNA into cells while preserving the DNA from nuclease degradation. Our previous work on preparing diagnostically labeled SNAs was labor intensive, relatively low yielding, and costly. Here, we describe a straightforward and facile preparation for labeling SNAs with optical and MR imaging probes with significantly improved physical properties. The synthesis of Gd(III) labeled DNA Au nanoparticle conjugates is achieved by sequential conjugation of 3′-thiol-modified oligonucleotides and cofunctionalization of the particle surface with the subsequent addition of 1,2 diothiolate modified chelates of Gd(III) (abbreviated: DNA-GdIII@AuNP). This new generation of SNA conjugates has a 2-fold increase of DNA labeling and a 1.4-fold increase in Gd(III) loading compared to published constructs. Furthermore, the relaxivity (r1) is observed to increase 4.5-fold compared to the molecular dithiolane-Gd(III) complex, and 1.4-fold increase relative to previous particle constructs where the Gd(III) complexes were conjugated to the oligonucleotides rather than directly to the Au particle. Importantly, this simplified approach (2 steps) exploits the advantages of previous Gd(III) labeled SNA platforms; however, this new approach is scalable and eliminates modification of DNA for attaching the contrast agent, and the particles exhibit improved cell labeling.
UR - http://www.scopus.com/inward/record.url?scp=85055121606&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85055121606&partnerID=8YFLogxK
U2 - 10.1021/acs.bioconjchem.8b00504
DO - 10.1021/acs.bioconjchem.8b00504
M3 - Article
C2 - 30193061
AN - SCOPUS:85055121606
VL - 29
SP - 3544
EP - 3549
JO - Bioconjugate Chemistry
JF - Bioconjugate Chemistry
SN - 1043-1802
IS - 11
ER -