A decomposable and sono-enzyme co-triggered nanoparticle(p TCP-CR NP)with“AND gate”logic was synthesized,combining a meso–carboxyl-porphyrin-based sonosensitizer(5,10,15,20-tetrakis(carboxyl)porphyrin,TCP)and a thi...A decomposable and sono-enzyme co-triggered nanoparticle(p TCP-CR NP)with“AND gate”logic was synthesized,combining a meso–carboxyl-porphyrin-based sonosensitizer(5,10,15,20-tetrakis(carboxyl)porphyrin,TCP)and a thiophenyl-croconium(2,5-bis[(2-(2-(2-hydroxyethoxy)ethoxy)ethyl-4-carboxylate-piperidylamino)thiophenyl]-croconium,CR)via ester groups.TCP releases carbon monoxide(CO)under ultrasound(US)irradiation,offering both sonodynamic and gas therapy.CR decomposes into stronger reactive oxygen species(ROS)compared to oxygen-based radicals.The F?rster resonance energy transfer(FRET)effect between TCP and CR inhibits ROS and CO generation until triggered by tumor cell overexpressed carboxylesterase(CEs).p TCP-CR NPs“AND gate”logic ensures activation only in the presence of both CEs and US,targeting tumor cells while safety in normal tissues.The ROS and CO generation abilities,as well as the releasing of SO_(4)^(·-)have been systemically examined.p TCP-CR can be thoroughly decomposed into low-toxic molecules post the treatment,showing the safety with negligible phototoxic reactions.In vivo anti-cancer therapy has been evaluated using mice bearing hepatocellular carcinoma.展开更多
Numerous efforts have been devoted to altering the dynamic covalent linkers between the drug structural units in polyprodrugs from the viewpoint of molecular structure;however,the effect of their aggregation states ha...Numerous efforts have been devoted to altering the dynamic covalent linkers between the drug structural units in polyprodrugs from the viewpoint of molecular structure;however,the effect of their aggregation states has not yet been explored.Here,the effect of aggregation states on the in vitro drug release and cytotoxicity was investigated using a pH/glutathione(GSH)co-triggered degradable doxorubicin(DOX)-based polyprodrug(PDOX)as a model,which was synthesized by the facile polymerization of a pH/GSH dual-triggered dimeric prodrug(DDOX_(ss))and 2,2-dimethoxypropane(DMP)by forming acid-labile ketal bond.Owing to the pH/GSH dual-triggered disulfide/α-amide and acid-labile ketal linkers between the DOX structural units,the resultant PDOX exhibited excellent pH/GSH co-triggered DOX release.With a similar diameter,the PDOX-NPs1 nanomedicines via fast precipitation showed faster DOX release than PDOX-NPs2 via slow self-assembly,regardless of their polymerization degree(DP).The effect of aggregation states is expected to be a secondary strategy for a more desired tumor intracellular microenvironment-responsive drug delivery for tumor chemotherapy,in addition to the molecular structures of polyprodrugs as drug self-delivery systems(DSDSs).展开更多
在离散事件触发通讯机制(discrete event-triggered communication scheme,DETCS)下,针对一类存在执行器时变故障的系统,研究了非均匀传输NCS故障调节与通讯协同设计的问题.首先,基于系统等周期的采样数据,采用时延分析法和Lyapunov稳...在离散事件触发通讯机制(discrete event-triggered communication scheme,DETCS)下,针对一类存在执行器时变故障的系统,研究了非均匀传输NCS故障调节与通讯协同设计的问题.首先,基于系统等周期的采样数据,采用时延分析法和Lyapunov稳定性理论,给出了具有鲁棒H_∞性能的状态及故障估计观测器设计方法,实现了对系统状态及连续时变故障的快速准确估计;进一步在DETCS下,基于所获得的故障和状态信息,以求解LMI的方式给出了同时求取具有故障调节能力状态反馈增益矩阵与事件触发权矩阵的方法,实现了故障调节与通讯的协同设计;最后,通过仿真算例验证了所提方法的可行性和有效性.展开更多
基金supported by grants from the National Natural Science Foundation of China(No.22375027)the Natural Science Foundation of Jiangsu Province(Nos.BK20221265,BK20211100)+1 种基金the Fundamental Research Funds for the Central Universities(No.DUT23YG133)the Research Funds from Liaoning Cancer Hospital(No.2024ZLKF-35)。
文摘A decomposable and sono-enzyme co-triggered nanoparticle(p TCP-CR NP)with“AND gate”logic was synthesized,combining a meso–carboxyl-porphyrin-based sonosensitizer(5,10,15,20-tetrakis(carboxyl)porphyrin,TCP)and a thiophenyl-croconium(2,5-bis[(2-(2-(2-hydroxyethoxy)ethoxy)ethyl-4-carboxylate-piperidylamino)thiophenyl]-croconium,CR)via ester groups.TCP releases carbon monoxide(CO)under ultrasound(US)irradiation,offering both sonodynamic and gas therapy.CR decomposes into stronger reactive oxygen species(ROS)compared to oxygen-based radicals.The F?rster resonance energy transfer(FRET)effect between TCP and CR inhibits ROS and CO generation until triggered by tumor cell overexpressed carboxylesterase(CEs).p TCP-CR NPs“AND gate”logic ensures activation only in the presence of both CEs and US,targeting tumor cells while safety in normal tissues.The ROS and CO generation abilities,as well as the releasing of SO_(4)^(·-)have been systemically examined.p TCP-CR can be thoroughly decomposed into low-toxic molecules post the treatment,showing the safety with negligible phototoxic reactions.In vivo anti-cancer therapy has been evaluated using mice bearing hepatocellular carcinoma.
文摘Numerous efforts have been devoted to altering the dynamic covalent linkers between the drug structural units in polyprodrugs from the viewpoint of molecular structure;however,the effect of their aggregation states has not yet been explored.Here,the effect of aggregation states on the in vitro drug release and cytotoxicity was investigated using a pH/glutathione(GSH)co-triggered degradable doxorubicin(DOX)-based polyprodrug(PDOX)as a model,which was synthesized by the facile polymerization of a pH/GSH dual-triggered dimeric prodrug(DDOX_(ss))and 2,2-dimethoxypropane(DMP)by forming acid-labile ketal bond.Owing to the pH/GSH dual-triggered disulfide/α-amide and acid-labile ketal linkers between the DOX structural units,the resultant PDOX exhibited excellent pH/GSH co-triggered DOX release.With a similar diameter,the PDOX-NPs1 nanomedicines via fast precipitation showed faster DOX release than PDOX-NPs2 via slow self-assembly,regardless of their polymerization degree(DP).The effect of aggregation states is expected to be a secondary strategy for a more desired tumor intracellular microenvironment-responsive drug delivery for tumor chemotherapy,in addition to the molecular structures of polyprodrugs as drug self-delivery systems(DSDSs).
文摘在离散事件触发通讯机制(discrete event-triggered communication scheme,DETCS)下,针对一类存在执行器时变故障的系统,研究了非均匀传输NCS故障调节与通讯协同设计的问题.首先,基于系统等周期的采样数据,采用时延分析法和Lyapunov稳定性理论,给出了具有鲁棒H_∞性能的状态及故障估计观测器设计方法,实现了对系统状态及连续时变故障的快速准确估计;进一步在DETCS下,基于所获得的故障和状态信息,以求解LMI的方式给出了同时求取具有故障调节能力状态反馈增益矩阵与事件触发权矩阵的方法,实现了故障调节与通讯的协同设计;最后,通过仿真算例验证了所提方法的可行性和有效性.
