Cholecystokinin-B Receptor-Targeted Nanoparticle for Imaging and Detection of Precancerous Lesions in the Pancreas
Survival from pancreatic cancer remains extremely poor, in part because this malignancy is not diagnosed in the early stages, and precancerous pancreatic intraepithelial neoplasia (PanIN) lesions are not seen on routine radiographic imaging. Since the cholecystokinin-B receptor (CCK-BR) becomes over...
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| Format: | Article |
| Language: | English |
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MDPI AG
2021-11-01
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| Series: | Biomolecules |
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| Online Access: | https://www.mdpi.com/2218-273X/11/12/1766 |
| _version_ | 1797506475779686400 |
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| author | Jill P. Smith Hong Cao Elijah F. Edmondson Siva Sai Krishna Dasa Stephan T. Stern |
| author_facet | Jill P. Smith Hong Cao Elijah F. Edmondson Siva Sai Krishna Dasa Stephan T. Stern |
| author_sort | Jill P. Smith |
| collection | DOAJ |
| description | Survival from pancreatic cancer remains extremely poor, in part because this malignancy is not diagnosed in the early stages, and precancerous pancreatic intraepithelial neoplasia (PanIN) lesions are not seen on routine radiographic imaging. Since the cholecystokinin-B receptor (CCK-BR) becomes over-expressed in PanIN lesions, it may serve as a target for early detection. We developed a biodegradable fluorescent polyplex nanoparticle (NP) that selectively targets the CCK-BR. The NP was complexed to a fluorescent oligonucleotide with Alexa Fluor 647 for far-red imaging and to an oligonucleotide conjugated to Alexa Fluor 488 for localization by immunohistochemistry. Fluorescence was detected over the pancreas of five- to ten-month-old LSL-Kras<sup>G12D/+</sup>; <i>P48-Cre</i> (KC) mice only after the injection of the receptor target-specific NP and not after injection of untargeted NP. Ex vivo tissue imaging and selective immunohistochemistry confirmed particle localization only to PanIN lesions in the pancreas and not in other organs, supporting the tissue specificity. A human pancreas tissue microarray demonstrated immunoreactivity for the CCK-BR only in the PanIN lesions and not in normal pancreas tissue. The long-term goal would be to develop this imaging tool for screening human subjects at high risk for pancreatic cancer to enable early cancer detection. |
| first_indexed | 2024-03-10T04:33:10Z |
| format | Article |
| id | doaj.art-d3724f4e0c804cf68578043e5db77e33 |
| institution | Directory Open Access Journal |
| issn | 2218-273X |
| language | English |
| last_indexed | 2024-03-10T04:33:10Z |
| publishDate | 2021-11-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Biomolecules |
| spelling | doaj.art-d3724f4e0c804cf68578043e5db77e332023-11-23T03:58:51ZengMDPI AGBiomolecules2218-273X2021-11-011112176610.3390/biom11121766Cholecystokinin-B Receptor-Targeted Nanoparticle for Imaging and Detection of Precancerous Lesions in the PancreasJill P. Smith0Hong Cao1Elijah F. Edmondson2Siva Sai Krishna Dasa3Stephan T. Stern4Department of Medicine, Georgetown University, Washington, DC 20007, USADepartment of Medicine, Georgetown University, Washington, DC 20007, USAMolecular Pathology Laboratory, Frederick National Laboratory for Cancer Research, Frederick, MD 21701, USANanotechnology Characterization Laboratory, Cancer Research Technology Program, Frederick National Laboratory for Cancer Research Sponsored by the National Cancer Institute, Frederick, MD 21701, USANanotechnology Characterization Laboratory, Cancer Research Technology Program, Frederick National Laboratory for Cancer Research Sponsored by the National Cancer Institute, Frederick, MD 21701, USASurvival from pancreatic cancer remains extremely poor, in part because this malignancy is not diagnosed in the early stages, and precancerous pancreatic intraepithelial neoplasia (PanIN) lesions are not seen on routine radiographic imaging. Since the cholecystokinin-B receptor (CCK-BR) becomes over-expressed in PanIN lesions, it may serve as a target for early detection. We developed a biodegradable fluorescent polyplex nanoparticle (NP) that selectively targets the CCK-BR. The NP was complexed to a fluorescent oligonucleotide with Alexa Fluor 647 for far-red imaging and to an oligonucleotide conjugated to Alexa Fluor 488 for localization by immunohistochemistry. Fluorescence was detected over the pancreas of five- to ten-month-old LSL-Kras<sup>G12D/+</sup>; <i>P48-Cre</i> (KC) mice only after the injection of the receptor target-specific NP and not after injection of untargeted NP. Ex vivo tissue imaging and selective immunohistochemistry confirmed particle localization only to PanIN lesions in the pancreas and not in other organs, supporting the tissue specificity. A human pancreas tissue microarray demonstrated immunoreactivity for the CCK-BR only in the PanIN lesions and not in normal pancreas tissue. The long-term goal would be to develop this imaging tool for screening human subjects at high risk for pancreatic cancer to enable early cancer detection.https://www.mdpi.com/2218-273X/11/12/1766pancreatic cancercholecystokinin receptorfluorescenceimagingPanINs |
| spellingShingle | Jill P. Smith Hong Cao Elijah F. Edmondson Siva Sai Krishna Dasa Stephan T. Stern Cholecystokinin-B Receptor-Targeted Nanoparticle for Imaging and Detection of Precancerous Lesions in the Pancreas Biomolecules pancreatic cancer cholecystokinin receptor fluorescence imaging PanINs |
| title | Cholecystokinin-B Receptor-Targeted Nanoparticle for Imaging and Detection of Precancerous Lesions in the Pancreas |
| title_full | Cholecystokinin-B Receptor-Targeted Nanoparticle for Imaging and Detection of Precancerous Lesions in the Pancreas |
| title_fullStr | Cholecystokinin-B Receptor-Targeted Nanoparticle for Imaging and Detection of Precancerous Lesions in the Pancreas |
| title_full_unstemmed | Cholecystokinin-B Receptor-Targeted Nanoparticle for Imaging and Detection of Precancerous Lesions in the Pancreas |
| title_short | Cholecystokinin-B Receptor-Targeted Nanoparticle for Imaging and Detection of Precancerous Lesions in the Pancreas |
| title_sort | cholecystokinin b receptor targeted nanoparticle for imaging and detection of precancerous lesions in the pancreas |
| topic | pancreatic cancer cholecystokinin receptor fluorescence imaging PanINs |
| url | https://www.mdpi.com/2218-273X/11/12/1766 |
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