Gas therapy is emerging as a highly promising therapeutic strategy for cancer treatment.However,there are limitations,including the lack of targeted subcellular organelle accuracy and spatiotemporal release precision,...Gas therapy is emerging as a highly promising therapeutic strategy for cancer treatment.However,there are limitations,including the lack of targeted subcellular organelle accuracy and spatiotemporal release precision,associated with gas therapy.In this study,we developed a series of photoactivatable nitric oxide(NO)donors NRh-R-NO(R=Me,Et,Bn,iPr,and Ph)based on an N-nitrosated upconversion luminescent rhodamine scaffold.Under the irradiation of 808 nm light,only NRh-Ph-NO could effectively release NO and NRh-Ph with a significant turn-on frequency upconversion luminescence(FUCL)signal at 740 nm,ascribed to lower N-N bond dissociation energy.We also investigated the involved multistage near-infrared-controlled cascade release of gas therapy,including the NO released from NRh-Ph-NO along with one NRh-Ph molecule generation,the superoxide anion O_(2)^(⋅−)produced by the photodynamic therapy(PDT)effect of NRh-Ph,and highly toxic peroxynitrite anion(ONOO‒)generated from the co-existence of NO and O_(2)^(⋅−).After mild nano-modification,the nanogenerator(NRh-Ph-NO NPs)empowered with superior biocompatibility could target mitochondria.Under an 808 nm laser irradiation,NRh-Ph-NO NPs could induce NO/ROS to generate RNS,causing a decrease in the mitochondrial membrane potential and initiating apoptosis by caspase-3 activation,which further induced tumor immunogenic cell death(ICD).In vivo therapeutic results of NRh-Ph-NO NPs showed augmented RNS-potentiated gas therapy,demonstrating excellent biocompatibility and effective tumor inhibition guided by real-time FUCL imaging.Collectively,this versatile strategy defines the targeted RNS-mediated cancer therapy.展开更多
A photocleavable low-molecular-weight hydrogelator (LMWG) was synthesized based on coumarin derivative.~1H NMR and UV spectroscopy study suggested that the gelator had good gelling ability, and the driving force for t...A photocleavable low-molecular-weight hydrogelator (LMWG) was synthesized based on coumarin derivative.~1H NMR and UV spectroscopy study suggested that the gelator had good gelling ability, and the driving force for the gelation were hydrogen bonding and π-π stacking. This molecular hydrogel exhibited satisfied photocleavage at C-N bond in 7-amino coumarin with the light irradiation (365 nm,77.5 mW/cm^2). The promising photo-triggered drug release of antineoplastics cytarabine hydrochloride has been obtained, due to the photocleavage motived gel-sol transition.展开更多
Nitric oxide（NO） donors are versatile tools for nitric oxide biology. The biological response of NO is dependent on the transient concentration and the sustained duration. N-Nitrosated rhodamines are photo-triggered...Nitric oxide（NO） donors are versatile tools for nitric oxide biology. The biological response of NO is dependent on the transient concentration and the sustained duration. N-Nitrosated rhodamines are photo-triggered and photo-calibrated NO donors. We recently discovered that suppression of the dihedral angle between the N-nitroso fragment with the rhodamine scaffold facilitates NO release.Inspired by this discovery, we developed a fast-releasing NO donor （NOD575） suitable for biological applications, e.g., the pulmonary arterial smooth muscle cells（PASMCs）.展开更多
Controllable profragrance nanoparticles are in great demand for long-lasting scent in flavor and fragrance industries.However,the practical applications of controllable fragrance release are limited by the non-tunable...Controllable profragrance nanoparticles are in great demand for long-lasting scent in flavor and fragrance industries.However,the practical applications of controllable fragrance release are limited by the non-tunable size,structural heterogeneity and poor reproducibility.Herein,a coumarin-derived phototrigger(CM-OH)is covalently conjugated with alcohol fragrances to obtain the corresponding profragrances(CM-R)which enable to release fragrances under the light controlling conditions.Furthermore,we introduce a new engineering strategy to construct fine tunable and highly uniform profragrance nanoparticles with flash nanoprecipitation(FNP)technology,which features commercial available amphiphilic pluronic F127 polymers by encapsulation of photoactivatable profragrances CM-R in hydrophobic cores to enhance the long-lasting photo-controllable fragrance release.With the assistance of FNP technology,amphiphilic pluronic polymer and profragrances CM-R in organic solution are instantaneously mixed and subsequently precipitated in the multi-inlet vortex mixer(MIVM),thus obtaining the pluronic F127-encapsulated profragrance nanoparticles with good homogeneity.Compared to the traditional thermodynamic encapsulation method,the novel kinetic FNP technology can not only tune the size of profragrance nanoparticles with narrow distribution,but also distinctly improve the batch-to-batch reproducibility,which affords an alternative method for scale-up preparation of amphiphilic profragrance nanoparticles in precisely controllable fragrance delivery system.展开更多
基金This work was financially supported by the National Natural Science Foundation of China(82272148,China)the“Double First-Class”University Project(CPUQNJC22-03,China)+4 种基金the Jiangsu Funding Program for Excellent Postdoctoral Talent(2022ZB301,China)the National University of Singapore(NUHSRO/2020/133/Startup/08,NUHSRO/2023/008/NUSMed/TCE/LOA,NUHSRO/2021/034/TRP/09/Nanomedicine)National Medical Research Council(MOH-OFIRG23jan-0005,CG21APR1005)Singapore Ministry of Education(MOE-000387-00)National Research Foundation(NRF-000352-00).
文摘Gas therapy is emerging as a highly promising therapeutic strategy for cancer treatment.However,there are limitations,including the lack of targeted subcellular organelle accuracy and spatiotemporal release precision,associated with gas therapy.In this study,we developed a series of photoactivatable nitric oxide(NO)donors NRh-R-NO(R=Me,Et,Bn,iPr,and Ph)based on an N-nitrosated upconversion luminescent rhodamine scaffold.Under the irradiation of 808 nm light,only NRh-Ph-NO could effectively release NO and NRh-Ph with a significant turn-on frequency upconversion luminescence(FUCL)signal at 740 nm,ascribed to lower N-N bond dissociation energy.We also investigated the involved multistage near-infrared-controlled cascade release of gas therapy,including the NO released from NRh-Ph-NO along with one NRh-Ph molecule generation,the superoxide anion O_(2)^(⋅−)produced by the photodynamic therapy(PDT)effect of NRh-Ph,and highly toxic peroxynitrite anion(ONOO‒)generated from the co-existence of NO and O_(2)^(⋅−).After mild nano-modification,the nanogenerator(NRh-Ph-NO NPs)empowered with superior biocompatibility could target mitochondria.Under an 808 nm laser irradiation,NRh-Ph-NO NPs could induce NO/ROS to generate RNS,causing a decrease in the mitochondrial membrane potential and initiating apoptosis by caspase-3 activation,which further induced tumor immunogenic cell death(ICD).In vivo therapeutic results of NRh-Ph-NO NPs showed augmented RNS-potentiated gas therapy,demonstrating excellent biocompatibility and effective tumor inhibition guided by real-time FUCL imaging.Collectively,this versatile strategy defines the targeted RNS-mediated cancer therapy.
基金financial support from the National Natural Science Foundation of China (Nos. 21672164, 21372177)
文摘A photocleavable low-molecular-weight hydrogelator (LMWG) was synthesized based on coumarin derivative.~1H NMR and UV spectroscopy study suggested that the gelator had good gelling ability, and the driving force for the gelation were hydrogen bonding and π-π stacking. This molecular hydrogel exhibited satisfied photocleavage at C-N bond in 7-amino coumarin with the light irradiation (365 nm,77.5 mW/cm^2). The promising photo-triggered drug release of antineoplastics cytarabine hydrochloride has been obtained, due to the photocleavage motived gel-sol transition.
基金financially supported by the National Natural Science Foundation of China (No. 21572061)the Fundamental Research Funds for the Central Universities (No. WY1516017)
文摘Nitric oxide（NO） donors are versatile tools for nitric oxide biology. The biological response of NO is dependent on the transient concentration and the sustained duration. N-Nitrosated rhodamines are photo-triggered and photo-calibrated NO donors. We recently discovered that suppression of the dihedral angle between the N-nitroso fragment with the rhodamine scaffold facilitates NO release.Inspired by this discovery, we developed a fast-releasing NO donor （NOD575） suitable for biological applications, e.g., the pulmonary arterial smooth muscle cells（PASMCs）.
基金support provided by National Key Research and Development Program(2016YFA0200300)NSFC Science Center Program(21788102)+3 种基金Creative Research Groups(21421004)NSFC/China(21636002 and 21622602)Shanghai Municipal Science and Technology Major Project(2018SHZDZX03)Program of Introducing Talents of Discipline to Universities(B16017).
文摘Controllable profragrance nanoparticles are in great demand for long-lasting scent in flavor and fragrance industries.However,the practical applications of controllable fragrance release are limited by the non-tunable size,structural heterogeneity and poor reproducibility.Herein,a coumarin-derived phototrigger(CM-OH)is covalently conjugated with alcohol fragrances to obtain the corresponding profragrances(CM-R)which enable to release fragrances under the light controlling conditions.Furthermore,we introduce a new engineering strategy to construct fine tunable and highly uniform profragrance nanoparticles with flash nanoprecipitation(FNP)technology,which features commercial available amphiphilic pluronic F127 polymers by encapsulation of photoactivatable profragrances CM-R in hydrophobic cores to enhance the long-lasting photo-controllable fragrance release.With the assistance of FNP technology,amphiphilic pluronic polymer and profragrances CM-R in organic solution are instantaneously mixed and subsequently precipitated in the multi-inlet vortex mixer(MIVM),thus obtaining the pluronic F127-encapsulated profragrance nanoparticles with good homogeneity.Compared to the traditional thermodynamic encapsulation method,the novel kinetic FNP technology can not only tune the size of profragrance nanoparticles with narrow distribution,but also distinctly improve the batch-to-batch reproducibility,which affords an alternative method for scale-up preparation of amphiphilic profragrance nanoparticles in precisely controllable fragrance delivery system.
