Cooperative nanomaterial system to sensitize, target, and treat tumors
A significant barrier to the clinical translation of systemically administered therapeutic nanoparticles is their tendency to be removed from circulation by the mononuclear phagocyte system. The addition of a targeting ligand that selectively interacts with cancer cells can improve the therapeutic e...
| Main Authors: | , , , , , , , |
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| Format: | Article |
| Language: | English |
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Proceedings of the National Academy of Sciences
2022
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| Online Access: | https://hdl.handle.net/1721.1/132161.2 |
| _version_ | 1810991274473291776 |
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| author | Park, Ji-Ho von Maltzhan, Geoffrey Xu, Mary Jue Fogal, Valentina Kotamraju, Venkata Ramana Ruoslahti, Erkki Bhatia, Sangeeta N Sailor, Michael J. |
| author2 | Harvard University--MIT Division of Health Sciences and Technology |
| author_facet | Harvard University--MIT Division of Health Sciences and Technology Park, Ji-Ho von Maltzhan, Geoffrey Xu, Mary Jue Fogal, Valentina Kotamraju, Venkata Ramana Ruoslahti, Erkki Bhatia, Sangeeta N Sailor, Michael J. |
| author_sort | Park, Ji-Ho |
| collection | MIT |
| description | A significant barrier to the clinical translation of systemically administered therapeutic nanoparticles is their tendency to be removed from circulation by the mononuclear phagocyte system. The addition of a targeting ligand that selectively interacts with cancer cells can improve the therapeutic efficacy of nanomaterials, although these systems have met with only limited success. Here, we present a cooperative nanosystem consisting of two discrete nanomaterials. The first component is gold nanorod (NR) "activators" that populate the porous tumor vessels and act as photothermal antennas to specify tumor heating via remote near-infrared laser irradiation. We find that local tumor heating accelerates the recruitment of the second component: a targeted nanoparticle consisting of either magnetic nanoworms (NW) or doxorubicinloaded liposomes (LP). The targeting species employed in this work is a cyclic nine-amino acid peptide LyP-1 (Cys-Gly-Asn-Lys-Arg-Thr-Arg-Gly-Cys) that binds to the stress-related protein, p32, which we find to be upregulated on the surface of tumor-associated cells upon thermal treatment. Mice containing xenografted MDA-MB-435 tumors that are treated with the combined NR/LyP-1LP therapeutic system display significant reductions in tumor volume compared with individual nanoparticles or untargeted cooperative system. |
| first_indexed | 2024-09-23T12:51:05Z |
| format | Article |
| id | mit-1721.1/132161.2 |
| institution | Massachusetts Institute of Technology |
| language | English |
| last_indexed | 2024-09-23T12:51:05Z |
| publishDate | 2022 |
| publisher | Proceedings of the National Academy of Sciences |
| record_format | dspace |
| spelling | mit-1721.1/132161.22022-07-25T20:31:52Z Cooperative nanomaterial system to sensitize, target, and treat tumors Park, Ji-Ho von Maltzhan, Geoffrey Xu, Mary Jue Fogal, Valentina Kotamraju, Venkata Ramana Ruoslahti, Erkki Bhatia, Sangeeta N Sailor, Michael J. Harvard University--MIT Division of Health Sciences and Technology Massachusetts Institute of Technology. Department of Electrical Engineering and Computer Science A significant barrier to the clinical translation of systemically administered therapeutic nanoparticles is their tendency to be removed from circulation by the mononuclear phagocyte system. The addition of a targeting ligand that selectively interacts with cancer cells can improve the therapeutic efficacy of nanomaterials, although these systems have met with only limited success. Here, we present a cooperative nanosystem consisting of two discrete nanomaterials. The first component is gold nanorod (NR) "activators" that populate the porous tumor vessels and act as photothermal antennas to specify tumor heating via remote near-infrared laser irradiation. We find that local tumor heating accelerates the recruitment of the second component: a targeted nanoparticle consisting of either magnetic nanoworms (NW) or doxorubicinloaded liposomes (LP). The targeting species employed in this work is a cyclic nine-amino acid peptide LyP-1 (Cys-Gly-Asn-Lys-Arg-Thr-Arg-Gly-Cys) that binds to the stress-related protein, p32, which we find to be upregulated on the surface of tumor-associated cells upon thermal treatment. Mice containing xenografted MDA-MB-435 tumors that are treated with the combined NR/LyP-1LP therapeutic system display significant reductions in tumor volume compared with individual nanoparticles or untargeted cooperative system. 2022-07-25T20:31:51Z 2021-09-20T18:21:12Z 2022-07-25T20:31:51Z 2010 2019-05-09T15:21:16Z Article http://purl.org/eprint/type/JournalArticle https://hdl.handle.net/1721.1/132161.2 en 10.1073/pnas.0909565107 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/octet-stream Proceedings of the National Academy of Sciences PNAS |
| spellingShingle | Park, Ji-Ho von Maltzhan, Geoffrey Xu, Mary Jue Fogal, Valentina Kotamraju, Venkata Ramana Ruoslahti, Erkki Bhatia, Sangeeta N Sailor, Michael J. Cooperative nanomaterial system to sensitize, target, and treat tumors |
| title | Cooperative nanomaterial system to sensitize, target, and treat tumors |
| title_full | Cooperative nanomaterial system to sensitize, target, and treat tumors |
| title_fullStr | Cooperative nanomaterial system to sensitize, target, and treat tumors |
| title_full_unstemmed | Cooperative nanomaterial system to sensitize, target, and treat tumors |
| title_short | Cooperative nanomaterial system to sensitize, target, and treat tumors |
| title_sort | cooperative nanomaterial system to sensitize target and treat tumors |
| url | https://hdl.handle.net/1721.1/132161.2 |
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