α[subscript v]β[subscript 3] Integrin-Targeted PLGA-PEG Nanoparticles for Enhanced Anti-tumor Efficacy of a Pt(IV) Prodrug
Targeted delivery of therapeutics to tumor neovasculature is potentially a powerful approach for selective cancer treatment. Integrins are heterodimeric transmembrane proteins involved in cell adhesion and cell signaling, and their expression is commonly upregulated in cancers and inflammatory disea...
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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/1721.1/78874 https://orcid.org/0000-0002-2693-4982 |
| _version_ | 1811068697312231424 |
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| author | Graf, Nora Bielenberg, Diane R. Kolishetti, Nagesh Muus, Christoph Banyard, Jacqueline Farokhzad, Omid C. Lippard, Stephen J. |
| author2 | Massachusetts Institute of Technology. Department of Chemistry |
| author_facet | Massachusetts Institute of Technology. Department of Chemistry Graf, Nora Bielenberg, Diane R. Kolishetti, Nagesh Muus, Christoph Banyard, Jacqueline Farokhzad, Omid C. Lippard, Stephen J. |
| author_sort | Graf, Nora |
| collection | MIT |
| description | Targeted delivery of therapeutics to tumor neovasculature is potentially a powerful approach for selective cancer treatment. Integrins are heterodimeric transmembrane proteins involved in cell adhesion and cell signaling, and their expression is commonly upregulated in cancers and inflammatory diseases. The α[subscript v]β[subscript 3] integrin is differentially upregulated on angiogenic endothelial cells as well as on many cancer cells. Here we demonstrate the differential targeting of cisplatin prodrug-encapsulated poly(d,l-lactic-co-glycolic acid)-block-polyethylene glycol (PLGA-PEG) nanoparticles (NPs) to the α[subscript v]β[subscript 3] integrin on cancer cells using the cyclic pentapeptide c(RGDfK). Cisplatin is one of the most widely used anticancer drugs, and approaches that can improve its therapeutic index are of broad importance. The RGD-targeted Pt(IV)-encapsulated NPs displayed enhanced cytotoxicity as compared to cisplatin administered in its conventional dosage form in model prostate and breast cancer epithelial cells in vitro. Cytotoxicities were also elevated in comparison to those of previously reported systems, a small molecule Pt(IV)-RGD conjugate and a Pt(IV) nanoscale coordination polymer carrying RGD moieties. This result encouraged us also to evaluate the anticancer effect of the new construct in an animal model. The RGD-targeted PLGA-PEG NPs were more efficacious and better tolerated by comparison to cisplatin in an orthotopic human breast cancer xenograft model in vivo. |
| first_indexed | 2024-09-23T07:59:46Z |
| format | Article |
| id | mit-1721.1/78874 |
| institution | Massachusetts Institute of Technology |
| language | en_US |
| last_indexed | 2024-09-23T07:59:46Z |
| publishDate | 2013 |
| publisher | American Chemical Society (ACS) |
| record_format | dspace |
| spelling | mit-1721.1/788742022-09-23T10:09:27Z α[subscript v]β[subscript 3] Integrin-Targeted PLGA-PEG Nanoparticles for Enhanced Anti-tumor Efficacy of a Pt(IV) Prodrug Graf, Nora Bielenberg, Diane R. Kolishetti, Nagesh Muus, Christoph Banyard, Jacqueline Farokhzad, Omid C. Lippard, Stephen J. Massachusetts Institute of Technology. Department of Chemistry Lippard, Stephen J. Graf, Nora Muus, Christoph Lippard, Stephen J. Targeted delivery of therapeutics to tumor neovasculature is potentially a powerful approach for selective cancer treatment. Integrins are heterodimeric transmembrane proteins involved in cell adhesion and cell signaling, and their expression is commonly upregulated in cancers and inflammatory diseases. The α[subscript v]β[subscript 3] integrin is differentially upregulated on angiogenic endothelial cells as well as on many cancer cells. Here we demonstrate the differential targeting of cisplatin prodrug-encapsulated poly(d,l-lactic-co-glycolic acid)-block-polyethylene glycol (PLGA-PEG) nanoparticles (NPs) to the α[subscript v]β[subscript 3] integrin on cancer cells using the cyclic pentapeptide c(RGDfK). Cisplatin is one of the most widely used anticancer drugs, and approaches that can improve its therapeutic index are of broad importance. The RGD-targeted Pt(IV)-encapsulated NPs displayed enhanced cytotoxicity as compared to cisplatin administered in its conventional dosage form in model prostate and breast cancer epithelial cells in vitro. Cytotoxicities were also elevated in comparison to those of previously reported systems, a small molecule Pt(IV)-RGD conjugate and a Pt(IV) nanoscale coordination polymer carrying RGD moieties. This result encouraged us also to evaluate the anticancer effect of the new construct in an animal model. The RGD-targeted PLGA-PEG NPs were more efficacious and better tolerated by comparison to cisplatin in an orthotopic human breast cancer xenograft model in vivo. National Cancer Institute (U.S.) (Grant CA034992) 2013-05-14T13:49:29Z 2013-05-14T13:49:29Z 2012-05 Article http://purl.org/eprint/type/JournalArticle 1936-0851 1936-086X http://hdl.handle.net/1721.1/78874 Graf, Nora, Diane R. Bielenberg, Nagesh Kolishetti, et al. α[subscript v]β[subscript 3] Integrin-Targeted PLGA-PEG Nanoparticles for Enhanced Anti-tumor Efficacy of a Pt(IV) Prodrug. ACS Nano 6(5): 4530–4539, 2012. https://orcid.org/0000-0002-2693-4982 en_US http://dx.doi.org/10.1021/nn301148e ACS Nano Creative Commons Attribution-Noncommercial-Share Alike 3.0 http://creativecommons.org/licenses/by-nc-sa/3.0/ application/pdf American Chemical Society (ACS) Prof. Lippard via Erja Kajosalo |
| spellingShingle | Graf, Nora Bielenberg, Diane R. Kolishetti, Nagesh Muus, Christoph Banyard, Jacqueline Farokhzad, Omid C. Lippard, Stephen J. α[subscript v]β[subscript 3] Integrin-Targeted PLGA-PEG Nanoparticles for Enhanced Anti-tumor Efficacy of a Pt(IV) Prodrug |
| title | α[subscript v]β[subscript 3] Integrin-Targeted PLGA-PEG Nanoparticles for Enhanced Anti-tumor Efficacy of a Pt(IV) Prodrug |
| title_full | α[subscript v]β[subscript 3] Integrin-Targeted PLGA-PEG Nanoparticles for Enhanced Anti-tumor Efficacy of a Pt(IV) Prodrug |
| title_fullStr | α[subscript v]β[subscript 3] Integrin-Targeted PLGA-PEG Nanoparticles for Enhanced Anti-tumor Efficacy of a Pt(IV) Prodrug |
| title_full_unstemmed | α[subscript v]β[subscript 3] Integrin-Targeted PLGA-PEG Nanoparticles for Enhanced Anti-tumor Efficacy of a Pt(IV) Prodrug |
| title_short | α[subscript v]β[subscript 3] Integrin-Targeted PLGA-PEG Nanoparticles for Enhanced Anti-tumor Efficacy of a Pt(IV) Prodrug |
| title_sort | α subscript v β subscript 3 integrin targeted plga peg nanoparticles for enhanced anti tumor efficacy of a pt iv prodrug |
| url | http://hdl.handle.net/1721.1/78874 https://orcid.org/0000-0002-2693-4982 |
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