Polyvalent Oligonucleotide Gold Nanoparticle Conjugates as Delivery Vehicles for Platinum(IV) Warheads
Amine-functionalized polyvalent oligonucleotide gold nanoparticles (DNA-Au NPs) were derivatized with a cisplatin prodrug, and the resulting DNA-Au NP conjugates were used to internalize multiple platinum centers. A platinum(IV) complex, c,c,t-[Pt(NH[subscript 3])[subscript 2]Cl[subscript 2](OH)(O[s...
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| Format: | Article |
| Language: | en_US |
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American Chemical Society (ACS)
2013
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| Online Access: | http://hdl.handle.net/1721.1/82149 https://orcid.org/0000-0002-2693-4982 |
| _version_ | 1826217417481650176 |
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| author | Dhar, Shanta Daniel, Weston L. Giljohann, David A. Mirkin, Chad A. Lippard, Stephen J. |
| author2 | Massachusetts Institute of Technology. Department of Chemistry |
| author_facet | Massachusetts Institute of Technology. Department of Chemistry Dhar, Shanta Daniel, Weston L. Giljohann, David A. Mirkin, Chad A. Lippard, Stephen J. |
| author_sort | Dhar, Shanta |
| collection | MIT |
| description | Amine-functionalized polyvalent oligonucleotide gold nanoparticles (DNA-Au NPs) were derivatized with a cisplatin prodrug, and the resulting DNA-Au NP conjugates were used to internalize multiple platinum centers. A platinum(IV) complex, c,c,t-[Pt(NH[subscript 3])[subscript 2]Cl[subscript 2](OH)(O[subscript 2]CCH[subscript 2]CH[subscript 2]CO[subscript 2]H)], was tethered to the surface of DNA-Au NPs through amide linkages. The platinum-tethered gold nanoparticles were taken into several cancer cells. The drop in intracellular pH facilitated reductive release of cisplatin from the prodrug, which then formed 1,2-d(GpG) intrastrand cross-links in the cell nuclei, as confirmed by an antibody specific for this adduct. The cytotoxicity of the platinum(IV) complex increases significantly in several cancer cell lines when the complex is attached to the surface of the DNA-Au NPs and in some instances exceeds that of cisplatin. |
| first_indexed | 2024-09-23T17:03:19Z |
| format | Article |
| id | mit-1721.1/82149 |
| institution | Massachusetts Institute of Technology |
| language | en_US |
| last_indexed | 2024-09-23T17:03:19Z |
| publishDate | 2013 |
| publisher | American Chemical Society (ACS) |
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| spelling | mit-1721.1/821492022-09-29T23:19:57Z Polyvalent Oligonucleotide Gold Nanoparticle Conjugates as Delivery Vehicles for Platinum(IV) Warheads Dhar, Shanta Daniel, Weston L. Giljohann, David A. Mirkin, Chad A. Lippard, Stephen J. Massachusetts Institute of Technology. Department of Chemistry Dhar, Shanta Daniel, Weston L. Lippard, Stephen J. Amine-functionalized polyvalent oligonucleotide gold nanoparticles (DNA-Au NPs) were derivatized with a cisplatin prodrug, and the resulting DNA-Au NP conjugates were used to internalize multiple platinum centers. A platinum(IV) complex, c,c,t-[Pt(NH[subscript 3])[subscript 2]Cl[subscript 2](OH)(O[subscript 2]CCH[subscript 2]CH[subscript 2]CO[subscript 2]H)], was tethered to the surface of DNA-Au NPs through amide linkages. The platinum-tethered gold nanoparticles were taken into several cancer cells. The drop in intracellular pH facilitated reductive release of cisplatin from the prodrug, which then formed 1,2-d(GpG) intrastrand cross-links in the cell nuclei, as confirmed by an antibody specific for this adduct. The cytotoxicity of the platinum(IV) complex increases significantly in several cancer cell lines when the complex is attached to the surface of the DNA-Au NPs and in some instances exceeds that of cisplatin. National Cancer Institute (U.S.) (Grant CA034992) National Cancer Institute (U.S.) (MIT-Harvard Center for Cancer Nanotechnology Excellence 5U54CA11934) David H. Koch Institute for Integrative Cancer Research at MIT 2013-11-18T13:18:42Z 2013-11-18T13:18:42Z 2009-09 2009-08 Article http://purl.org/eprint/type/JournalArticle 0002-7863 1520-5126 http://hdl.handle.net/1721.1/82149 Dhar, Shanta, Weston L. Daniel, David A. Giljohann, Chad A. Mirkin, and Stephen J. Lippard. “Polyvalent Oligonucleotide Gold Nanoparticle Conjugates as Delivery Vehicles for Platinum(IV) Warheads.” Journal of the American Chemical Society 131, no. 41 (October 21, 2009): 14652-14653. https://orcid.org/0000-0002-2693-4982 en_US http://dx.doi.org/10.1021/ja9071282 Journal of the American Chemical Society Article is made available in accordance with the publisher's policy and may be subject to US copyright law. Please refer to the publisher's site for terms of use. application/pdf American Chemical Society (ACS) PMC |
| spellingShingle | Dhar, Shanta Daniel, Weston L. Giljohann, David A. Mirkin, Chad A. Lippard, Stephen J. Polyvalent Oligonucleotide Gold Nanoparticle Conjugates as Delivery Vehicles for Platinum(IV) Warheads |
| title | Polyvalent Oligonucleotide Gold Nanoparticle Conjugates as Delivery Vehicles for Platinum(IV) Warheads |
| title_full | Polyvalent Oligonucleotide Gold Nanoparticle Conjugates as Delivery Vehicles for Platinum(IV) Warheads |
| title_fullStr | Polyvalent Oligonucleotide Gold Nanoparticle Conjugates as Delivery Vehicles for Platinum(IV) Warheads |
| title_full_unstemmed | Polyvalent Oligonucleotide Gold Nanoparticle Conjugates as Delivery Vehicles for Platinum(IV) Warheads |
| title_short | Polyvalent Oligonucleotide Gold Nanoparticle Conjugates as Delivery Vehicles for Platinum(IV) Warheads |
| title_sort | polyvalent oligonucleotide gold nanoparticle conjugates as delivery vehicles for platinum iv warheads |
| url | http://hdl.handle.net/1721.1/82149 https://orcid.org/0000-0002-2693-4982 |
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