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

Abstract

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.

Imidazole–carbazole conjugate for two-photon-excited photodynamic therapy and fluorescence bioimaging

“…Thus, imidazolium was converted to thionate forms to harvest an enhanced ISC process and ROS generation. 5 As expected, the singlet oxygen production of RSS ( Φ Δ > 0.6) was higher than that of RIS . However, RSS exhibited a weak emission ( Φ F < 0.01).…”

“…In recent years, several heavy-atom-free PSs were developed by replacing oxygen with a sulfur atom in carbonyl fluorophores. 5 Sulfur-substituted PSs exhibited excellent ROS generation due to the efficient enhancement of the ISC process but their fluorescence emission was quenched, limiting their phototheranostic application. In principle, fluorescence is emitted from excited singlet states to the ground state via radiative deactivation, and 1 O 2 is generated from the energy transfer of excited triplet states with oxygen molecules.…”

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

“…Cell experiments, confocal microscopy cell imaging, and cell viability experiments were performed following previous reports …”

“…In the realm of PSs, the incorporation of heavy atoms has traditionally been pursued to enhance intersystem crossing (ISC) processes, thereby promoting ROS generation. − However, concerns surrounding the cost and dark toxicity associated with heavy atoms have driven researchers to explore alternative molecular designs that employ heavy-atom-free PSs. − Recent advancements have focused on strategies such as thionation-enhanced spin–orbit coupling (SOC), ,, reduction of singlet–triplet energy gap (Δ E S–T ), − and enhanced ISC process by charge recombination, , twisted π-systems, or radical. − Despite the significant improvements achieved in triplet formation and 1 O 2 generation, heavy-atom-free PSs often exhibit low or quenched fluorescence emission, limiting their suitability for fluorescence bioimaging applications. This phenomenon can be attributed to a negative correlation between radiative decay and the ISC process, where energy is dissipated through nonradiative decay pathways .…”

“…5−10 However, concerns surrounding the cost and dark toxicity associated with heavy atoms have driven researchers to explore alternative molecular designs that employ heavy-atom-free PSs. 11−13 Recent advancements have focused on strategies such as thionation-enhanced spin−orbit coupling (SOC), 11,14,15 reduction of singlet−triplet energy gap (ΔE S−T ), 16−18 and enhanced ISC process by charge recombination, 19,20 twisted π-systems, 21 or radical. 22−24 Despite the significant improvements achieved in triplet formation and 1 O 2 generation, heavy-atom-free PSs often exhibit low or quenched fluorescence emission, limiting their suitability for fluorescence bioimaging applications.…”