Rationally designed monoamine oxidase A‐activatable AIE molecular photosensitizer for the specific imaging and cellular therapy of tumors

Abstract

Due to both the requirements of repeated complex organic synthesis and tedious biochemical verification experiments for the screening of new photosensitizers, the development of a satisfactory photosensitizer with excellent photosensitivity and highly specific response ability is still a great challenge for the accurate imaging localization and the precise photodynamic therapy (PDT) of tumors. Herein, under the help of theoretical calculations, a high‐efficient target‐activatable aggregation‐induced emission (AIE) molecular photosensitizer, TPE‐TThPy, is rationally designed and synthesized by the conjugation of tetraphenylethylene (TPE, which is used as the electron donor) and tetrahydropyridine (ThPy, which can be converted to methylpyridine salts as the electron acceptor) using thiophene (T) as the π‐bridge. This TPE‐TThPy molecule exhibits not only good cellular uptake and mitochondrial targeting ability but also ultra‐high monoamine oxidase A (MAO‐A) response specificity and excellent photosensitivity when oxidized under the action of MAO‐A. The specifically imaging ability and cellular PDT performance of the MOA‐A‐activatable AIE photosensitizer of TPE‐TThPy is demonstrated by using different cell lines and mouse tumor models. The successful development of this MOA‐A‐activatable AIE photosensitizer also provides insight for the development of single‐molecule PDT therapeutic drugs with excellent photosensitivity and highly specific targeting‐response ability.

Novel aggregation-induced emission-photosensitizers with built-in capability of mitochondria targeting and glutathione depletion for efficient photodynamic therapy

“…These results demonstrate that AIE-PS NPs effectively damaged the mitochondria and showed potential for mitochondria-targeting PDT. 33 Moreover, for efficacious PDT, it is necessary that photosensitizers should generate ROS effectively in the vicinity of cellular organelles. As discussed previouly in sections ROS and 1 O 2 generation efficacy of AIE-PS NPs and Intracellular ROS production, both TPEPy-BA NPs and TPEPy-BE NPs showed excellent ROS efficiency with mitochondria-targeting ability.…”

Self-Assembly Mitochondria-Targeting Donor–Acceptor Type Theranostic Nanosphere Activates ROS Storm for Multimodal Cancer Therapy

“…In general, chromophores with typical electron donor–acceptor (D–A) structures were beneficial to red-shift absorption/emission wavelength and generate ROS upon photoirradiation. ,, Inspired by this principle, a series of D–A molecules with a distinct length of the alkyl chain, named TPA-N- n ( n = 4/8/12), were successfully synthesized (Scheme ). The twisted triphenylamine (TPA) structure as the electron donor could work as a rotor to regulate the movement of molecules in the aggregated state.…”

“…According to the previous reports, the smaller energy gap (E g ) between the highest occupied molecular orbital (HOMO) and the lowest unoccupied molecular orbital (LUMO) would be beneficial for the ROS generation. 18,21,22 Density functional theory (DFT) calculations suggested that the electron cloud in the HOMO orbit was mainly distributed on the TPA unit and slightly delocalized to the benzothiadiazole block, while the LUMO was mainly determined by the styrylpyridine cation (Figures 1f and S14). The spatial separation of HOMO and LUMO confirmed the existence of ICT transition, where the electrons could transfer from donor TPA to acceptors benzothiadiazole and styrylpyridine cation.…”

Cationic AIE-active photosensitizers for highly efficient photodynamic eradication of drug-resistant bacteria

“…21 In addition, most PSs including these newly emerged type I PSs with planar structures suffer from a p-p stacking associated aggregation-caused quenching (ACQ) effect, resulting in unacceptable fluorescence quenching as well as low ROS efficiency in the aggregated state or high concentrations such as enriching in infected areas, which seriously hinders the clinical application of PDT antimicrobials. 22,23 The concept of aggregation-induced emission (AIE) established in 2001 offers a novel solution to organic fluorophores and PSs. 24 Quite different from these ACQ molecules, AIE-active fluorogens (AIEgens) show negligible fluorescence in the molecular state, but emit amplified fluorescence in the aggregated state because the nonradiative pathway is interrupted by the restriction of intramolecular motion (RIM), which also leads to promoted ISC processes as well.…”

“…21 In addition, most PSs including these newly emerged type I PSs with planar structures suffer from a π–π stacking associated aggregation-caused quenching (ACQ) effect, resulting in unacceptable fluorescence quenching as well as low ROS efficiency in the aggregated state or high concentrations such as enriching in infected areas, which seriously hinders the clinical application of PDT antimicrobials. 22,23…”