Dual anticancer and antibacterial activity of fluorescent naphthoimidazolium salts.

Cancer has emerged as a significant global health challenge, ranking as the second leading cause of death worldwide. Moreover, cancer patients frequently experience compromised immune systems, rendering them susceptible to bacterial infections. Combining anticancer and antibacterial properties in a single drug could lead to improved overall treatment outcomes and patient well-being. In this context, the present study focused on a series of hydrophilic naphthoimidazolium salts with donor groups (NI-R), aiming to create dual-functional agents with antibacterial and anticancer activities. Among these compounds, NI-TPA demonstrated notable antibacterial activity, particularly against drug-resistant bacteria, with MIC value of 7.8 µg mL-1. Furthermore, NI-TPA exhibited the most potent cytotoxicity against four different cancer cell lines, with an IC50 range of 0.67-2.01 µg mL-1. The observed high cytotoxicity of NI-TPA agreed with molecular docking and dynamic simulation studies targeting c-Met kinase protein. Additionally, NI-TPA stood out as the most promising candidate for two-photo excitation, fluorescence bioimaging, and localization in lysosomes. The study findings open new avenues for the design and development of imidazolium salts that could be employed in phototheranostic applications for cancer treatment and bacterial infections.

Imidazolium-Based Heavy-Atom-Free Photosensitizer for Nucleus-Targeted Fluorescence Bioimaging and Photodynamic Therapy.

The development of heavy-atom-free photosensitizers (PSs) for photodynamic therapy (PDT) has encountered significant challenges in achieving simultaneous high fluorescence emission and reactive oxygen species (ROS) generation. Moreover, the limited water solubility of these PSs imposes further limitations on their biomedical applications. To overcome these obstacles, this study presents a molecular design strategy employing hydrophilic heavy-atom-free PSs based on imidazolium salts. The photophysical properties of these PSs were comprehensively investigated through a combination of experimental and theoretical analyses. Notably, among the synthesized PSs, the ethylcarbazole-naphthoimidazolium (NI-Cz) conjugate exhibited efficient fluorescence emission (ΦF = 0.22) and generation of singlet oxygen (ΦΔ = 0.49), even in highly aqueous environments. The performance of NI-Cz was validated through its application in fluorescence bioimaging and PDT treatment in HeLa cells. Furthermore, NI-Cz holds promise for two-photon excitation and type I ROS generation, nucleus localization, and selective activity against Gram-positive bacteria, thereby expanding its scope for the design of heavy-atom-free PSs and phototheranostic applications.

Dual Molecular Design toward a Lysosome-Tagged AIEgen and Heavy-Atom-Free Photosensitizers for Hypoxic Cancer Photodynamic Therapy.

To date, a large number of photosensitizers (PS) have introduced heavy atoms to improve the ISC process and 1O2 generation. However, they often show low efficiency in hypoxic conditions, aggregate states, and turn-off PDT in the dark. Besides that, the toxicity of heavy metals is also concerned. Therefore, we developed lysosome-targeted heavy-metal-free PS (3S and 4S) based on thionated naphthalimide for hypoxic cancer photodynamic therapy (PDT), not only under white light but also in the dark via thermal-induced 1O2 generation. AIEgen (3O and 4O) were prepared for studying the PDT action of PSs (3S and 4S) in lysosome and aggregate state. We also examined the photophysical properties of AIEgen (3O and 4O) and PS (3S and 4S) by UV-vis absorption, fluorescent emission spectra, and theoretical calculations.