Photodynamic therapy(PDT)as a non-invasive anticancer modality has received increasing attention due to its advantages of noninvasiveness,high temporospatial selectivity,simple and controllable operation,etc.PDT mainl...Photodynamic therapy(PDT)as a non-invasive anticancer modality has received increasing attention due to its advantages of noninvasiveness,high temporospatial selectivity,simple and controllable operation,etc.PDT mainly relies on the generation of toxic reactive oxygen species(ROS)by photosensitizers(PSs)under the light irradiation to cause cancer cell apoptosis and death.However,solid tumors usually exhibit an inherent hypoxic microenvironment,which greatly limits the PDT efficacy of these high oxygen-dependent conventional type II PSs.Therefore,it is of great importance to design and develop efficient type I PSs that are less oxygen-dependent for the treatment of hypoxic tumors.Herein,a new strategy for the preparation of efficient type I PSs by introducing the photoinduced electron transfer(PET)mechanism is reported.DR-NO_(2) is obtained by introducing 4-nitrobenzyl to(Z)-2-(5-(4-(diethylamino)-2-hydroxybenzylidene)-4-oxo-3-phenylthiazolidin-2-ylidene)malononitrile(DR-OH)with aggregation-induced emission(AIE)feature.The AIE feature ensures their high ROS generation efficiency in aggregate,and the PET process leads to fluorescence quenching of DR-NO_(2) to promote triplet state formation,which also promotes intramolecular charge separation and electron transfer that is conducive for type I ROS particularly superoxide radicals generation.In addition,DR-NO_(2) nanoparticles are prepared by nanoprecipitation to possess nanoscaled sizes,high cancer cell uptake,and excellent type I ROS generation ability,which results in an excellent performance in PDT ablation of MCF-7 cancer cells.This PET strategy for the development of type I PSs possesses great potential for PDT applications against hypoxic tumors.展开更多
Three nanostructured photosensitizers with aggregation-induced emission(AIE) characteristics based on2,3-bis(4?-(diphenylamino)-[1,1?-biphenyl]-4-yl) fumaronitrile(BDBF) were prepared for image-guided photodynamic the...Three nanostructured photosensitizers with aggregation-induced emission(AIE) characteristics based on2,3-bis(4?-(diphenylamino)-[1,1?-biphenyl]-4-yl) fumaronitrile(BDBF) were prepared for image-guided photodynamic therapy(PDT). BDBF was encapsulated with Pluronic F-127(F127) to form usual spherical nanoparticles(F127@BDBF NPs) with a red fluorescence emission and 9.8% fluorescence quantum yield(FQY). Moreover, BDBF self-assembled into nanorods(BDBF NRs) in water. Compared with F127@BDBF NPs, BDBF NRs exhibited stronger orange fluorescence with a higher FQY of 23.3% and similar singlet oxygen(1O2) generation capability. BDBF NRs were further modified with F127 to form BDBF@F127 NRs with the same 1O2 generation ability as BDBF NRs. The three nanostructures exhibited a higher 1O2 production capacity than BDBF molecule in dissolved state and favorable stability in an aqueous solution as well as under physiological condition. In vitro photocytotoxicity experiments indicated that the three nanostructures inhibited tumor cell proliferation effectively.Therefore, to construct eligible nanostructures with a high FQY and 1O2 generation ability, simple self-assembly can serve as a valuable method to prepare photosensitizers with enhanced PDT.展开更多
文摘Photodynamic therapy(PDT)as a non-invasive anticancer modality has received increasing attention due to its advantages of noninvasiveness,high temporospatial selectivity,simple and controllable operation,etc.PDT mainly relies on the generation of toxic reactive oxygen species(ROS)by photosensitizers(PSs)under the light irradiation to cause cancer cell apoptosis and death.However,solid tumors usually exhibit an inherent hypoxic microenvironment,which greatly limits the PDT efficacy of these high oxygen-dependent conventional type II PSs.Therefore,it is of great importance to design and develop efficient type I PSs that are less oxygen-dependent for the treatment of hypoxic tumors.Herein,a new strategy for the preparation of efficient type I PSs by introducing the photoinduced electron transfer(PET)mechanism is reported.DR-NO_(2) is obtained by introducing 4-nitrobenzyl to(Z)-2-(5-(4-(diethylamino)-2-hydroxybenzylidene)-4-oxo-3-phenylthiazolidin-2-ylidene)malononitrile(DR-OH)with aggregation-induced emission(AIE)feature.The AIE feature ensures their high ROS generation efficiency in aggregate,and the PET process leads to fluorescence quenching of DR-NO_(2) to promote triplet state formation,which also promotes intramolecular charge separation and electron transfer that is conducive for type I ROS particularly superoxide radicals generation.In addition,DR-NO_(2) nanoparticles are prepared by nanoprecipitation to possess nanoscaled sizes,high cancer cell uptake,and excellent type I ROS generation ability,which results in an excellent performance in PDT ablation of MCF-7 cancer cells.This PET strategy for the development of type I PSs possesses great potential for PDT applications against hypoxic tumors.
基金financially supported by the National Natural Science Foundation of China (21835001, 51773080, 21674041, 51573068, 21221063, and 81870117)the Program for Changbaishan Scholars of Jilin Province, Jilin Province project (20160101305JC)+1 种基金Jilin Province Science and Technology Development Plan (20190201252JC)“Talents Cultivation Program” of Jilin University
文摘Three nanostructured photosensitizers with aggregation-induced emission(AIE) characteristics based on2,3-bis(4?-(diphenylamino)-[1,1?-biphenyl]-4-yl) fumaronitrile(BDBF) were prepared for image-guided photodynamic therapy(PDT). BDBF was encapsulated with Pluronic F-127(F127) to form usual spherical nanoparticles(F127@BDBF NPs) with a red fluorescence emission and 9.8% fluorescence quantum yield(FQY). Moreover, BDBF self-assembled into nanorods(BDBF NRs) in water. Compared with F127@BDBF NPs, BDBF NRs exhibited stronger orange fluorescence with a higher FQY of 23.3% and similar singlet oxygen(1O2) generation capability. BDBF NRs were further modified with F127 to form BDBF@F127 NRs with the same 1O2 generation ability as BDBF NRs. The three nanostructures exhibited a higher 1O2 production capacity than BDBF molecule in dissolved state and favorable stability in an aqueous solution as well as under physiological condition. In vitro photocytotoxicity experiments indicated that the three nanostructures inhibited tumor cell proliferation effectively.Therefore, to construct eligible nanostructures with a high FQY and 1O2 generation ability, simple self-assembly can serve as a valuable method to prepare photosensitizers with enhanced PDT.