An acceptor-shielding strategy of photosensitizers for enhancing the generation efficiency of type I reactive oxygen species and the related photodynamic immunotherapy

Abstract

Developing efficient photosensitizers (PSs) that can generate Type I reactive oxygen species (ROS) under illumination, is considered an effective way to improve photodynamic therapy (PDT) outcomes due to the hypoxic...

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

“…This demonstrated that the connection of the styrylpyridine cation could enhance the ICT between the strong donor TPA and the intermediate acceptor benzothiadiazole. The emission peaks of TPA-N- n ( n = 4/8/12) were similar to each other, which demonstrated that the existence of alkyl side chain could only affect the molecular conformation, not the electron distribution. , …”

“…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.…”

“…The emission peaks of TPA-N-n (n = 4/8/12) were similar to each other, which demonstrated that the existence of alkyl side chain could only affect the molecular conformation, not the electron distribution. 15,16 The AIE properties of TPA-N-n were further examined. Fluorophores TPA-N-n showed weak fluorescence in DMSO, while the fluorescence intensity was much enhanced upon the addition of water, indicating that TPA-N-n owned obvious AIE properties (Figure 1d and Figure S9).…”

“…On the other hand, due to the hypoxic condition of the solid tumor, reactive oxygen species (ROS) of O 2 • – and OH• were preferential, which were not dependent on the concentration of O 2 . , However, the generation of O 2 • – and OH• for the reported theranostic agents were mediated under the external activation (such as photoirradiation). − Under this circumstance, we have designed a series of AIE theranostic agents, TPA-N- n ( n = 4, 8, 12) with few considerations (Scheme ): (1) the existence of twisted TPA ensured the AIE properties; (2) the electron donor TPA and the acceptor benzothiadiazole were directly connected to construct D–A structure, realize the ICT, and facilitate the ROS production; (3) styrylpyridine cation could target to the mitochondria and enhance the ICT effect as a further electron acceptor; (4) the long alkyl chain could tune the molecule packing mode and the permeability to cells. ,, …”

“…(2) the electron donor TPA and the acceptor benzothiadiazole were directly connected to construct D−A structure, realize the ICT, and facilitate the ROS production; (3) styrylpyridine cation could target to the mitochondria and enhance the ICT effect as a further electron acceptor; (4) the long alkyl chain could tune the molecule packing mode and the permeability to cells. 4,15,16 In this work, with the appropriate alkyl chain length (n = 8), complex TPA-N-8 had the best cytotoxicity to cancerous HeLa cells with an IC 50 value of 4.3 μM and could be self-assembled to a nanosphere with a diameter of 161.2 nm in the DMSO/ PBS solution. It is worth noting that TPA-N-8 could accumulate in the mitochondria and produce major ROS species O 2 • − and OH• as well as a small amount of 1 O 2 without photoirradiation.…”