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Article

NIR Photodynamic Destruction of PDAC and HNSCC Nodules Using Triple-Receptor-Targeted Photoimmuno-Nanoconjugates: Targeting Heterogeneity in Cancer

by
Shazia Bano
1,†,
Girgis Obaid
1,2,†,
Joseph W. R. Swain
1,
Marina Yamada
1,3,
Brian W. Pogue
4,
Kenneth Wang
5 and
Tayyaba Hasan
1,6,*
1
Wellman Center for Photomedicine, Massachusetts General Hospital and Harvard Medical School, Boston, MA 02114, USA
2
Department of Bioengineering, The University of Texas at Dallas, Richardson, TX 75080, USA
3
Department of Health Sciences, Northeastern University, Boston, MA 02115, USA
4
Thayer School of Engineering, Dartmouth College, Hanover, New Hampshire 03755, USA
5
Division of Gastroenterology and Hepatology, Mayo Clinic, Rochester, MN 55905, USA
6
Division of Health Sciences and Technology, Harvard University and Massachusetts Institute of Technology, Cambridge, MA 02139, USA
*
Author to whom correspondence should be addressed.
†
Both authors contributed equally to the work.
J. Clin. Med. 2020, 9(8), 2390; https://doi.org/10.3390/jcm9082390
Submission received: 9 July 2020 / Accepted: 17 July 2020 / Published: 27 July 2020
(This article belongs to the Special Issue The Past, Present and Future of Photodynamic Therapy for Cancers)
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Abstract

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.
Keywords: intratumoral heterogeneity; biomarkers; multiple receptor-targeting; cetuximab; holo-transferrin; trastuzumab intratumoral heterogeneity; biomarkers; multiple receptor-targeting; cetuximab; holo-transferrin; trastuzumab

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MDPI and ACS Style

Bano, S.; Obaid, G.; Swain, J.W.R.; Yamada, M.; Pogue, B.W.; Wang, K.; Hasan, T. NIR Photodynamic Destruction of PDAC and HNSCC Nodules Using Triple-Receptor-Targeted Photoimmuno-Nanoconjugates: Targeting Heterogeneity in Cancer. J. Clin. Med. 2020, 9, 2390. https://doi.org/10.3390/jcm9082390

AMA Style

Bano S, Obaid G, Swain JWR, Yamada M, Pogue BW, Wang K, Hasan T. NIR Photodynamic Destruction of PDAC and HNSCC Nodules Using Triple-Receptor-Targeted Photoimmuno-Nanoconjugates: Targeting Heterogeneity in Cancer. Journal of Clinical Medicine. 2020; 9(8):2390. https://doi.org/10.3390/jcm9082390

Chicago/Turabian Style

Bano, Shazia, Girgis Obaid, Joseph W. R. Swain, Marina Yamada, Brian W. Pogue, Kenneth Wang, and Tayyaba Hasan. 2020. "NIR Photodynamic Destruction of PDAC and HNSCC Nodules Using Triple-Receptor-Targeted Photoimmuno-Nanoconjugates: Targeting Heterogeneity in Cancer" Journal of Clinical Medicine 9, no. 8: 2390. https://doi.org/10.3390/jcm9082390

APA Style

Bano, S., Obaid, G., Swain, J. W. R., Yamada, M., Pogue, B. W., Wang, K., & Hasan, T. (2020). NIR Photodynamic Destruction of PDAC and HNSCC Nodules Using Triple-Receptor-Targeted Photoimmuno-Nanoconjugates: Targeting Heterogeneity in Cancer. Journal of Clinical Medicine, 9(8), 2390. https://doi.org/10.3390/jcm9082390

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