NIR Photodynamic Destruction of PDAC and HNSCC Nodules Using Triple-Receptor-Targeted Photoimmuno-Nanoconjugates: Targeting Heterogeneity in Cancer
Receptor heterogeneity in cancer is a major limitation of molecular targeting for cancer therapeutics. Single-receptor-targeted treatment exerts selection pressures that result in treatment escape for low-receptor-expressing tumor subpopulations. To overcome this potential for heterogeneity-driven r...
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doaj-5b096276765d425ba4a267fc34c3d23b2020-11-25T02:36:36ZengMDPI AGJournal of Clinical Medicine2077-03832020-07-0192390239010.3390/jcm9082390NIR Photodynamic Destruction of PDAC and HNSCC Nodules Using Triple-Receptor-Targeted Photoimmuno-Nanoconjugates: Targeting Heterogeneity in CancerShazia Bano0Girgis Obaid1Joseph W. R. Swain2Marina Yamada3Brian W. Pogue4Kenneth Wang5Tayyaba Hasan6Wellman Center for Photomedicine, Massachusetts General Hospital and Harvard Medical School, Boston, MA 02114, USAWellman Center for Photomedicine, Massachusetts General Hospital and Harvard Medical School, Boston, MA 02114, USAWellman Center for Photomedicine, Massachusetts General Hospital and Harvard Medical School, Boston, MA 02114, USAWellman Center for Photomedicine, Massachusetts General Hospital and Harvard Medical School, Boston, MA 02114, USAThayer School of Engineering, Dartmouth College, Hanover, NH 03755, USADivision of Gastroenterology and Hepatology, Mayo Clinic, Rochester, MN 55905, USAWellman Center for Photomedicine, Massachusetts General Hospital and Harvard Medical School, Boston, MA 02114, USAReceptor heterogeneity in cancer is a major limitation of molecular targeting for cancer therapeutics. Single-receptor-targeted treatment exerts selection pressures that result in treatment escape for low-receptor-expressing tumor subpopulations. To overcome this potential for heterogeneity-driven resistance to molecular targeted photodynamic therapy (PDT), we present for the first time a triple-receptor-targeted photoimmuno-nanoconjugate (TR-PIN) platform. TR-PIN functionalization with cetuximab, holo-transferrin, and trastuzumab conferred specificity for epidermal growth factor receptor (EGFR), transferrin receptor (TfR), and human epidermal growth factor receptor 2 (HER-2), respectively. The TR-PINs exhibited up to a 24-fold improvement in cancer cell binding compared with EGFR-specific cetuximab-targeted PINs (Cet-PINs) in low-EGFR-expressing cell lines. Photodestruction using TR-PINs was significantly higher than the monotargeted Cet-PINs in heterocellular 3D in vitro models of heterogeneous pancreatic ductal adenocarcinoma (PDAC; MIA PaCa-2 cells) and heterogeneous head and neck squamous cell carcinoma (HNSCC, SCC9 cells) containing low-EGFR-expressing T47D (high TfR) or SKOV-3 (high HER-2) cells. Through their capacity for multiple tumor target recognition, TR-PINs can serve as a unique and amenable platform for the effective photodynamic eradication of diverse tumor subpopulations in heterogeneous cancers to mitigate escape for more complete and durable treatment responses.https://www.mdpi.com/2077-0383/9/8/2390intratumoral heterogeneitybiomarkersmultiple receptor-targetingcetuximabholo-transferrintrastuzumab |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Shazia Bano Girgis Obaid Joseph W. R. Swain Marina Yamada Brian W. Pogue Kenneth Wang Tayyaba Hasan |
spellingShingle |
Shazia Bano Girgis Obaid Joseph W. R. Swain Marina Yamada Brian W. Pogue Kenneth Wang Tayyaba Hasan NIR Photodynamic Destruction of PDAC and HNSCC Nodules Using Triple-Receptor-Targeted Photoimmuno-Nanoconjugates: Targeting Heterogeneity in Cancer Journal of Clinical Medicine intratumoral heterogeneity biomarkers multiple receptor-targeting cetuximab holo-transferrin trastuzumab |
author_facet |
Shazia Bano Girgis Obaid Joseph W. R. Swain Marina Yamada Brian W. Pogue Kenneth Wang Tayyaba Hasan |
author_sort |
Shazia Bano |
title |
NIR Photodynamic Destruction of PDAC and HNSCC Nodules Using Triple-Receptor-Targeted Photoimmuno-Nanoconjugates: Targeting Heterogeneity in Cancer |
title_short |
NIR Photodynamic Destruction of PDAC and HNSCC Nodules Using Triple-Receptor-Targeted Photoimmuno-Nanoconjugates: Targeting Heterogeneity in Cancer |
title_full |
NIR Photodynamic Destruction of PDAC and HNSCC Nodules Using Triple-Receptor-Targeted Photoimmuno-Nanoconjugates: Targeting Heterogeneity in Cancer |
title_fullStr |
NIR Photodynamic Destruction of PDAC and HNSCC Nodules Using Triple-Receptor-Targeted Photoimmuno-Nanoconjugates: Targeting Heterogeneity in Cancer |
title_full_unstemmed |
NIR Photodynamic Destruction of PDAC and HNSCC Nodules Using Triple-Receptor-Targeted Photoimmuno-Nanoconjugates: Targeting Heterogeneity in Cancer |
title_sort |
nir photodynamic destruction of pdac and hnscc nodules using triple-receptor-targeted photoimmuno-nanoconjugates: targeting heterogeneity in cancer |
publisher |
MDPI AG |
series |
Journal of Clinical Medicine |
issn |
2077-0383 |
publishDate |
2020-07-01 |
description |
Receptor heterogeneity in cancer is a major limitation of molecular targeting for cancer therapeutics. Single-receptor-targeted treatment exerts selection pressures that result in treatment escape for low-receptor-expressing tumor subpopulations. To overcome this potential for heterogeneity-driven resistance to molecular targeted photodynamic therapy (PDT), we present for the first time a triple-receptor-targeted photoimmuno-nanoconjugate (TR-PIN) platform. TR-PIN functionalization with cetuximab, holo-transferrin, and trastuzumab conferred specificity for epidermal growth factor receptor (EGFR), transferrin receptor (TfR), and human epidermal growth factor receptor 2 (HER-2), respectively. The TR-PINs exhibited up to a 24-fold improvement in cancer cell binding compared with EGFR-specific cetuximab-targeted PINs (Cet-PINs) in low-EGFR-expressing cell lines. Photodestruction using TR-PINs was significantly higher than the monotargeted Cet-PINs in heterocellular 3D in vitro models of heterogeneous pancreatic ductal adenocarcinoma (PDAC; MIA PaCa-2 cells) and heterogeneous head and neck squamous cell carcinoma (HNSCC, SCC9 cells) containing low-EGFR-expressing T47D (high TfR) or SKOV-3 (high HER-2) cells. Through their capacity for multiple tumor target recognition, TR-PINs can serve as a unique and amenable platform for the effective photodynamic eradication of diverse tumor subpopulations in heterogeneous cancers to mitigate escape for more complete and durable treatment responses. |
topic |
intratumoral heterogeneity biomarkers multiple receptor-targeting cetuximab holo-transferrin trastuzumab |
url |
https://www.mdpi.com/2077-0383/9/8/2390 |
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