Epidermal Growth Factor Receptor-Targeted Multifunctional Photosensitizers for Bladder Cancer Imaging and Photodynamic Therapy
| Autor: | Shunichi Fukuzumi, Ravindra Pandey, Dhyan Chandra, Ramona Watson, Joseph R. Missert, Munawwar Sajjad, Rutao Yao, Farukh A. Durrani, Rajesh Kumar, Mohamed E. El-Khouly, Ravindra R. Cheruku, Aimee J. Marko, Joseph Cacaccio, Khurshid A. Guru, Walter A. Tabaczynski |
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| Rok vydání: | 2019 |
| Předmět: |
medicine.medical_treatment
Antineoplastic Agents Apoptosis Photodynamic therapy Mice SCID 01 natural sciences Article Erlotinib Hydrochloride Mice 03 medical and health sciences Epidermal growth factor In vivo Cell Line Tumor Drug Discovery medicine Animals Humans Epidermal growth factor receptor neoplasms 030304 developmental biology 0303 health sciences Photosensitizing Agents Bladder cancer biology Chemistry medicine.disease Xenograft Model Antitumor Assays respiratory tract diseases 0104 chemical sciences ErbB Receptors 010404 medicinal & biomolecular chemistry Photochemotherapy Urinary Bladder Neoplasms Positron-Emission Tomography Cancer research biology.protein Molecular Medicine Erlotinib medicine.drug Conjugate |
| Zdroj: | J Med Chem |
| ISSN: | 1520-4804 0022-2623 |
| DOI: | 10.1021/acs.jmedchem.8b01927 |
| Popis: | The in vitro and in vivo anticancer activity of iodinated photosensitizers (PSs) with and without an erlotinib moiety was investigated in UMUC3 [epidermal growth factor (EGFR)-positive] and T24 (EGFR-low) cell lines and tumored mice. Both the erlotinib-conjugated PSs 3 and 5 showed EGFR target specificity, but the position-3 erlotinib-PS conjugate 3 demonstrated lower photodynamic therapy efficacy than the corresponding non-erlotinib analogue 1, whereas the conjugate 5 containing an erlotinib moiety at position-17 of the PS showed higher tumor uptake and long-term tumor cure (severe combined immunodeficient mice bearing UMUC3 tumors). PS-erlotinib conjugates in the absence of light were ineffective in vitro and in vivo, but robust apoptotic and necrotic cell death was observed in bladder cancer cells after exposing them to a laser light at 665 nm. In contrast to 18F-fluorodeoxyglucose, a positron emission tomography agent, the position-17 erlotinib conjugate (124I-analogue 6) showed enhanced UMUC3 tumor contrast even at a low imaging dose of 15 μCi/mouse. |
| Databáze: | OpenAIRE |
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