Hydrogen as a therapeutic agent has attracted a great deal of attention because of its superior therapeutic outcome on many diseases,including inflammatory injury,tumors,metabolic disorders,and neurological diseases.P...Hydrogen as a therapeutic agent has attracted a great deal of attention because of its superior therapeutic outcome on many diseases,including inflammatory injury,tumors,metabolic disorders,and neurological diseases.Photocatalytic hydrogen evolution has emerged as a promising strategy for hydrogen production and delivery.This review article presents the recent developments in the design and synthesis of conjugated polymer materials,including linear polymers and crosslinked conjugated materials,for photocatalytic hydrogen evolution.Particularly,we focus this review on the development of conjugated polymers as photocatalysts and the resulting hydrogen therapy in the fields of anti-inflammatory,free radical scavenging,and cancer treatment.Finally,this article discusses the future research and perspective of conjugated polymer materials for hydrogen evolution and the potential clinical applications of hydrogen as a therapeutic agent.展开更多
Ultrasound(US)-activated sonodynamic therapy(SDT)stands for a distinct antitumor modality because of its attractive characteristics including intriguing noninvasiveness,desirable safety,and high tissue penetration dep...Ultrasound(US)-activated sonodynamic therapy(SDT)stands for a distinct antitumor modality because of its attractive characteristics including intriguing noninvasiveness,desirable safety,and high tissue penetration depth,which,unfortunately,suffers from compromised therapeutic efficacy due to cancer cell-inherent adaptive mechanisms,such as glutathione(GSH)neutralization response to reactive oxygen species(ROS),and glutamine addictive properties of tumors.In this work,we developed a biological sonosensitive platelet(PLT)pharmacytes for favoring US/GSH-responsive combinational therapeutic of glutamine deprivation and augmented SDT.The amino acid transporter SLC6A14 blockade agentα-methyl-DL-tryptophan(α-MT)-loaded and MnO_(2)-coated porphyrinic metal-organic framework(MOF)nanoparticles were encapsulated in the PLTs through the physical adsorption of electrostatic attraction and the intrinsic endocytosis of PLTs.When the sonosensitive PLT pharmacytes reached tumor sites through their natural tendencies to TME,US stimulated the PLTs-loaded porphyrinic MOF to generate ROS,resulting in morphological changes of the PLTs and the release of nanoparticles.Subsequently,intracellular high concentration of GSH and extracellular spatio-temporal controlled US irradiation programmatically triggered the release ofα-MT,which enabled the synergistically amplified SDT by inducing amino acid starvation,inhibiting mTOR,and mediating ferroptosis.In addition,US stimulation achieved the targeted activation of PLTs at tumor vascular site,which evolved from circulating PLTs to dendritic PLTs,effectively blocking the blood supply of tumors through thrombus formation,and revealing the encouraging potential to facilitate tumor therapeutics.展开更多
Malignant melanoma cell-intrinsic PD-1:PD-L1 interaction thrusts tumorigenesis,angiogenesis,and radioresistance via mTOR hyperactivation to aggravate circumjacent aggression.Interdicting melanoma intrinsic growth sign...Malignant melanoma cell-intrinsic PD-1:PD-L1 interaction thrusts tumorigenesis,angiogenesis,and radioresistance via mTOR hyperactivation to aggravate circumjacent aggression.Interdicting melanoma intrinsic growth signals,including the blockade of PD-L1 and mTOR signaling concurrently,cooperative with radiotherapy may provide a vigorous repertoire to alleviate the tumor encumbrance.Thence,we design a three-pronged platinum@polymer-catechol nanobraker to deliver mTOR inhibitor TAK228 and anti-PD-L1 antibody(aPD-L1)for impeding the melanoma-PD-1-driven aggression and maximizing the melanoma eradication.The aPD-L1 collaborated with TAK228 restrains melanoma cell-intrinsic PD-1:PD-L1 tumorigenic interaction via blocking melanoma-PD-L1 ligand and the melanoma-PD-1 receptor-driven mTOR signaling;corresponding downregulation of mTOR downstream protumorigenic cellular MYC and proangiogenic hypoxia-inducible factor 1-alpha is conducive to preventing tumorigenesis and angiogenesis,respectively.Further,high-Z metal platinum sensitizing TAK228-enhanced radiotherapy confers the nanobraker on remarkable tumoricidal efficacy.Hereto,the customized three-pronged nanobrakers efficiently suppress melanoma tumorigenesis and angiogenesis concomitant with the amplification of radiotherapeutic efficacy.Such an ingenious tactic may provide substantial benefits to clinical melanoma patients.展开更多
As a hybrid imaging technique, photoacoustic imaging （PAI） can provide multiscale morphological information of tissues, and the use of multi-spectral PAI （MSPAI） can recover the spatial distribution of chromophore...As a hybrid imaging technique, photoacoustic imaging （PAI） can provide multiscale morphological information of tissues, and the use of multi-spectral PAI （MSPAI） can recover the spatial distribution of chromophores of interest, such as hemoglobin within tissues. Herein, we developed a contrast agent that can very effectively combine multiscale PAI with MSPAI for a more comprehensive characterization of complex biological tissues. Specifically, we developed novel PIID-DTBT based semi-conducting polymer dots （Pdots） that show broad and strong optical absorption in the visible-light region （500-700 nm）. The performances of gold nanoparticles （GNPs） and gold nanorods （GNRs）, which have been verified as excellent photoacoustic contrast agents, were compared with that of the Pdots based on the multiscale PAI system. Both ex vivo and in vivo experiments demonstrated that the Pdots have better photoacoustic conversion efficiency at 532 nm than GNPs and showed similar photoacoustic performance with GNRs at 700 nm at the same mass concentration. Photostability and toxicity tests demonstrated that the Pdots are photostable and biocompatible. More importantly, an in vivo MSPAI experiment indicated that the Pdots have better photoacoustic performance than the blood and therefore the signals can be accurately extracted from the background of vascular-rich tissues. Our work demonstrates the great potential of Pdots as highly effective contrast agents for the precise localization of lesions relative to the blood vessels based on multiscale PAI and MSPAI.展开更多
Nanomedicine-assisted sonodynamic therapy(SDT)has emerged as one of the most promising cancer therapies due to its unique advantages of high pene-tration,non-radiation,and excellent oxidative stress effect,but has alw...Nanomedicine-assisted sonodynamic therapy(SDT)has emerged as one of the most promising cancer therapies due to its unique advantages of high pene-tration,non-radiation,and excellent oxidative stress effect,but has always suffered from the self-protection mechanism and apoptosis resistance char-acteristics of evolutionarily mutated cancer cells.Regulated cell death(RCD)has received increasing attention in precision cancer treatments because of its significant role in synergistically sensitizing apoptosis and reversing the immunosuppressive microenvironment during SDT nanomedicine-triggered immunogenic cell death.Herein,paradigmatic research of RCD-augmented sonodynamic tumor immunotherapeutics are typically introduced,such as autophagy blockade,ferroptosis targeting,pyroptosis induction,necroptosis initiation,cuproptosis actuation,PANoptosis trigger,and the coordinated anti-tumor mechanisms are discussed in detail.Multiple analysis focusing on the currently unsolved problems and future development prospects of RCD-based SDT nano-oncology medicine are also discussed and prospected to further strengthen and expand the scope of its therapeutic applications.展开更多
基金Guangdong Provincial Key Laboratory of Advanced Biomaterials,Grant/Award Number:2022B1212010003National Natural Science Foundation of China,Grant/Award Numbers:22204070,62235007+2 种基金National Key Research and Development Program of China,Grant/Award Number:2020YFA0909000Shenzhen Science and Technology Innovation Program,Grant/Award Numbers:JCYJ20210324115807021,KQTD20170810111314625,SGDX20211123114002003Shenzhen Bay Laboratory,Grant/Award Number:SZBL2021080601002。
文摘Hydrogen as a therapeutic agent has attracted a great deal of attention because of its superior therapeutic outcome on many diseases,including inflammatory injury,tumors,metabolic disorders,and neurological diseases.Photocatalytic hydrogen evolution has emerged as a promising strategy for hydrogen production and delivery.This review article presents the recent developments in the design and synthesis of conjugated polymer materials,including linear polymers and crosslinked conjugated materials,for photocatalytic hydrogen evolution.Particularly,we focus this review on the development of conjugated polymers as photocatalysts and the resulting hydrogen therapy in the fields of anti-inflammatory,free radical scavenging,and cancer treatment.Finally,this article discusses the future research and perspective of conjugated polymer materials for hydrogen evolution and the potential clinical applications of hydrogen as a therapeutic agent.
基金supported by the Science and Technology Development Fund,Macao SAR(Grant No.0114/2019/A2,0085/2020/A2)the Research Grant of University of Macao(Grant No.MYRG2020-00130-FHS).
文摘Ultrasound(US)-activated sonodynamic therapy(SDT)stands for a distinct antitumor modality because of its attractive characteristics including intriguing noninvasiveness,desirable safety,and high tissue penetration depth,which,unfortunately,suffers from compromised therapeutic efficacy due to cancer cell-inherent adaptive mechanisms,such as glutathione(GSH)neutralization response to reactive oxygen species(ROS),and glutamine addictive properties of tumors.In this work,we developed a biological sonosensitive platelet(PLT)pharmacytes for favoring US/GSH-responsive combinational therapeutic of glutamine deprivation and augmented SDT.The amino acid transporter SLC6A14 blockade agentα-methyl-DL-tryptophan(α-MT)-loaded and MnO_(2)-coated porphyrinic metal-organic framework(MOF)nanoparticles were encapsulated in the PLTs through the physical adsorption of electrostatic attraction and the intrinsic endocytosis of PLTs.When the sonosensitive PLT pharmacytes reached tumor sites through their natural tendencies to TME,US stimulated the PLTs-loaded porphyrinic MOF to generate ROS,resulting in morphological changes of the PLTs and the release of nanoparticles.Subsequently,intracellular high concentration of GSH and extracellular spatio-temporal controlled US irradiation programmatically triggered the release ofα-MT,which enabled the synergistically amplified SDT by inducing amino acid starvation,inhibiting mTOR,and mediating ferroptosis.In addition,US stimulation achieved the targeted activation of PLTs at tumor vascular site,which evolved from circulating PLTs to dendritic PLTs,effectively blocking the blood supply of tumors through thrombus formation,and revealing the encouraging potential to facilitate tumor therapeutics.
基金This work was supported by the National Natural Science Foundation of China(NSFC 32171318 and 32101069)the Faculty of Health Sciences,University of Macao,the Science and Technology Development Fund,Macao SAR(File no.0109/2018/A3,0011/2019/AKP,0113/2019/A2,0103/2021/A,and 0002/2021/AKP)+1 种基金the Multi-Year Research Grant(MYRG)of University of Macao(File no.MYRG2022-00011-FHS)Shenzhen Science and Technology Innovation Commission,Shenzhen-Hong Kong-Macao Science and Technology Plan C(No.SGDX20201103093600004).
文摘Malignant melanoma cell-intrinsic PD-1:PD-L1 interaction thrusts tumorigenesis,angiogenesis,and radioresistance via mTOR hyperactivation to aggravate circumjacent aggression.Interdicting melanoma intrinsic growth signals,including the blockade of PD-L1 and mTOR signaling concurrently,cooperative with radiotherapy may provide a vigorous repertoire to alleviate the tumor encumbrance.Thence,we design a three-pronged platinum@polymer-catechol nanobraker to deliver mTOR inhibitor TAK228 and anti-PD-L1 antibody(aPD-L1)for impeding the melanoma-PD-1-driven aggression and maximizing the melanoma eradication.The aPD-L1 collaborated with TAK228 restrains melanoma cell-intrinsic PD-1:PD-L1 tumorigenic interaction via blocking melanoma-PD-L1 ligand and the melanoma-PD-1 receptor-driven mTOR signaling;corresponding downregulation of mTOR downstream protumorigenic cellular MYC and proangiogenic hypoxia-inducible factor 1-alpha is conducive to preventing tumorigenesis and angiogenesis,respectively.Further,high-Z metal platinum sensitizing TAK228-enhanced radiotherapy confers the nanobraker on remarkable tumoricidal efficacy.Hereto,the customized three-pronged nanobrakers efficiently suppress melanoma tumorigenesis and angiogenesis concomitant with the amplification of radiotherapeutic efficacy.Such an ingenious tactic may provide substantial benefits to clinical melanoma patients.
基金Acknowledgements This study was supported by the University of Macao in Macao （Nos. MYRG2014-00093-FHS, MYRG 2015-00036-FHS, and MYRG2016-00110-FHS）, Macao government （Nos. FDCT 026/2014/A1 and FDCT 025/2015/A1）, and the National Natural Science Foundation of China （No. 11434017）.
文摘As a hybrid imaging technique, photoacoustic imaging （PAI） can provide multiscale morphological information of tissues, and the use of multi-spectral PAI （MSPAI） can recover the spatial distribution of chromophores of interest, such as hemoglobin within tissues. Herein, we developed a contrast agent that can very effectively combine multiscale PAI with MSPAI for a more comprehensive characterization of complex biological tissues. Specifically, we developed novel PIID-DTBT based semi-conducting polymer dots （Pdots） that show broad and strong optical absorption in the visible-light region （500-700 nm）. The performances of gold nanoparticles （GNPs） and gold nanorods （GNRs）, which have been verified as excellent photoacoustic contrast agents, were compared with that of the Pdots based on the multiscale PAI system. Both ex vivo and in vivo experiments demonstrated that the Pdots have better photoacoustic conversion efficiency at 532 nm than GNPs and showed similar photoacoustic performance with GNRs at 700 nm at the same mass concentration. Photostability and toxicity tests demonstrated that the Pdots are photostable and biocompatible. More importantly, an in vivo MSPAI experiment indicated that the Pdots have better photoacoustic performance than the blood and therefore the signals can be accurately extracted from the background of vascular-rich tissues. Our work demonstrates the great potential of Pdots as highly effective contrast agents for the precise localization of lesions relative to the blood vessels based on multiscale PAI and MSPAI.
基金This work was supported by the Science and Technology Development Fund,Macao SAR(File No.:0032/2023/ITP1)the Ministry of Education Frontiers Science Centre for Precision Oncology,University of Macao(SP2023-00001-FSCPO and FHS-FSCPO/011/2023)the National Natural Science Foundation of China(82302369).
文摘Nanomedicine-assisted sonodynamic therapy(SDT)has emerged as one of the most promising cancer therapies due to its unique advantages of high pene-tration,non-radiation,and excellent oxidative stress effect,but has always suffered from the self-protection mechanism and apoptosis resistance char-acteristics of evolutionarily mutated cancer cells.Regulated cell death(RCD)has received increasing attention in precision cancer treatments because of its significant role in synergistically sensitizing apoptosis and reversing the immunosuppressive microenvironment during SDT nanomedicine-triggered immunogenic cell death.Herein,paradigmatic research of RCD-augmented sonodynamic tumor immunotherapeutics are typically introduced,such as autophagy blockade,ferroptosis targeting,pyroptosis induction,necroptosis initiation,cuproptosis actuation,PANoptosis trigger,and the coordinated anti-tumor mechanisms are discussed in detail.Multiple analysis focusing on the currently unsolved problems and future development prospects of RCD-based SDT nano-oncology medicine are also discussed and prospected to further strengthen and expand the scope of its therapeutic applications.
