Small molecules may play a significant role as theranostic agents for the diagnosis and treatment of some severe disorders, such as cancer. A theranostic agent must have a therapeutic moiety, an imaging group for diagnostics, and a targeting portion for specific cell recognition. In this study, we synthesized two new molecules, D and E, as potential theranostic agents, consisting of a β-lactam portion acting as a selective α4β1 integrin agonist, a fluorescent imaging probe for diagnostics purposes, and a cytotoxic portion for anticancer activity. Compound D incorporates a 1,8-naphthylimide fluorophore for imaging and the 5-FU cytotoxic unit, whereas compound E features BODIPY moiety serving both as a photosensitizer and as a cytotoxic agent. Both compounds were evaluated for their photophysical properties. The binding assays for α4β1 integrin revealed that only E had a good affinity (KD 68.2 ± 1.0 μM). In adhesion assays with Jurkat E6.1, K562, HT-29, and HEK-293 cells, E retained the selective agonist activity for α4β1 integrin (EC50 0.92 ± 0.14 μM) as the parental β-lactam ligand A. Upon photosensitization, compound E induced a significant concentration-dependent reduction in cell viability across all tested cell lines, regardless of integrin expression. Internalization experiments indicated a nonselective cellular uptake of compound E, likely due to its high lipophilicity, which may outweigh the contribution of structural elements responsible for specific integrin recognition.
Giraldi et al. (Tue,) studied this question.