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Epidermal growth factor receptor (EGFR) and vascular endothelial growth factor receptor (VEGFR) are two extensively studied membrane-bound receptor tyrosine kinase proteins that are frequently overexpressed in many cancers. As a result, these receptor families constitute attractive targets for imaging and therapeutic applications in the detection and treatment of cancer. This review explores the dynamic structure and structure-function relationships of these two growth factor receptors and their significance as it relates to theranostics of cancer, followed by some of the common inhibition modalities frequently employed to target EGFR and VEGFR, such as tyrosine kinase inhibitors (TKIs), antibodies, nanobodies, and peptides. A summary of the recent advances in molecular imaging techniques, including positron emission tomography (PET), single-photon emission computerized tomography (SPECT), computed tomography (CT), magnetic resonance imaging (MRI), and optical imaging (OI), and in particular, near-IR fluorescence imaging using tetrapyrrolic-based fluorophores, concludes this review. 

Through a simple 1,3-cycloaddition reaction, three BODIPY-peptide conjugates that target the extracellular domain of the epidermal growth factor receptor (EGFR) were prepared and their ability for binding to EGFR was investigated. The peptide ligands K(N3)LARLLT and its cyclic analog cyclo(K(N3)larllt, previously shown to have high affinity for binding to the extracellular domain of EGFR, were conjugated to alkynyl-functionalized BODIPY dyes 1 and 2 via a copper-catalyzed click reaction. This reaction produced conjugates 3, 4, and 5 in high yields (70–82%). In vitro studies using human carcinoma HEp2 cells that overexpress EGFR demonstrated high cellular uptake, particularly for the cyclic peptide conjugate 5, and low cytotoxicity in light (~1 J·cm−2) and darkness. Surface plasmon resonance (SPR) results show binding affinity of the three BODIPY-peptide conjugates for EGFR, particularly for 5 bearing the cyclic peptide. Competitive binding studies using three cell lines with different expressions of EGFR show that 5 binds specifically to EGFR-overexpressing colon cancer cells. Among the three conjugates, 5 bearing the cyclic peptide exhibited the highest affinity for binding to the EGFR protein. 

Subphthalocyanine (SubPc) macrocycles are known as an interesting class of nonplanar aromatic dyes. Despite documented high fluorescence and singlet oxygen quantum yields, the properties of SubPcs in photodynamic therapy (PDT) are underestimated, because their absorption bands do not reach a significant wavelength range. With this in mind, we combined a SubPc ring and a SubPc ring by introducing a common benzene ring and obtained a SubPc dimer (2) and trimer (3) with the Q-band at the near-IR region, owing to the expansion of the [Formula: see text] electron conjugated system. In this study, we reported 1 O 2 generation abilities of 2 and 3based on the applied absolute singlet oxygen quantum yields ([Formula: see text] absolute ). Subsequent research revealed that 2 and 3 showed the potential to generate 1 O 2 to not only in toluene but also in DMSO. Although the photocytotoxicity of 2 and 3 were investigated upon photo-irradiation with a low light dose of approximately 1.5 J/cm 2 , 2 and 3 showed almost negligible toxic properties toward HEp2 cells.