Epidermal Growth Factor Receptor-Targeted Multifunctional Photosensitizers for Bladder Cancer Imaging and Photodynamic Therapy

Abstract

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.

EGFR-Targeted Photodynamic Therapy

“…Photosensitizers such as chlorines have fluorescence properties that are exploitable in imaging. Chlorine labelled with 124 I represents an innovative agent characterized by multimodal imaging (positron emission tomography (PET) and fluorescence) and therapeutic potential (PDT) [127]. The in vitro and in vivo anticancer activity and imaging properties of iodinated photosensitizers with and without erlotinib were investigated in EGFR-positive cell lines and tumorous mice [127].…”

“…Chlorine labelled with 124 I represents an innovative agent characterized by multimodal imaging (positron emission tomography (PET) and fluorescence) and therapeutic potential (PDT) [127]. The in vitro and in vivo anticancer activity and imaging properties of iodinated photosensitizers with and without erlotinib were investigated in EGFR-positive cell lines and tumorous mice [127]. The erlotinib-conjugated iodinated chlorine showed EGFR target specificity that improved both the phototoxicity and imaging properties [127].…”

“…The in vitro and in vivo anticancer activity and imaging properties of iodinated photosensitizers with and without erlotinib were investigated in EGFR-positive cell lines and tumorous mice [127]. The erlotinib-conjugated iodinated chlorine showed EGFR target specificity that improved both the phototoxicity and imaging properties [127]. On the other hand, an efficient synergistic therapy was developed by synthesizing a compound (NBSNe) that combined a PS moiety, Nile blue with S-substitution (NBS), and an EGFR tyrosine kinase inhibitor (EGFR-TKIs), neratinib (Ne) [128].…”

<p>Pathological Mechanism of Photodynamic Therapy and Photothermal Therapy Based on Nanoparticles</p>

“…Generally, it is divided into four categories: a) actively targeting functions, for example, take immune, 31 epidermal growth factor receptor (EGFR), low-density lipoprotein (LDL), mRNA, etc., as targeting. 32,33 b) It has functions of magnetic orientation and heat therapy: Fe 3 O 4 nanoparticles are widely used in hyperthermia (HPT) therapy for tumor tissues under direct current magnetic field. 34 HPT and PDT co-therapy have been successfully combined with HPD or zinc phthalocyanine, etc., in combination therapy.…”

Recent progress of hypoxia-modulated multifunctional nanomedicines to enhance photodynamic therapy: opportunities, challenges, and future development

“…Unfortunately, PDT still faces certain limitations, including the selection of effective photosensitizers, administration of light doses and the enormous limitation of tumor hypoxia 10 , 11 . Up to now, great strides and achievements have been made to conduct research on the photosensitizers and light doses 12 , 13 , 14 , 15 . However, there are still many challenges ahead of us in modulating hypoxia for enhancing PDT.…”