A nanomicelle(denoted as TPGS/Ppa)was fabricated via the coassembly of the amphiphilic D-α-tocopheryl polyethylene glycol 1000 succinate(TPGS)and the hydrophobic photosensitizer pyropheophorbide a(Ppa)for photodynami...A nanomicelle(denoted as TPGS/Ppa)was fabricated via the coassembly of the amphiphilic D-α-tocopheryl polyethylene glycol 1000 succinate(TPGS)and the hydrophobic photosensitizer pyropheophorbide a(Ppa)for photodynamic therapy(PDT).The obtained nanomicelle possessed a spherical structure with a diameter of(18.0±2.2)nm and a zeta potential of approximately -18 mV.Besides,the nanomicelle exhibited excellent photostability,biocompatibility,and phototoxicity,and could effectively reach the tumor region via the enhanced permeability and retention effect.Additionally,it could be found that the TPGS/Ppa nanomicelle exhibited higher phototoxicity against 4T1 murine mammary cancer cells than free Ppa.In the 4T1 tumor-bearing mouse model,the nanomicelle showed an excellent antitumor therapeutic effect.This study develops a new type of photodynamic nanomicelle TPGS/Ppa,which can increase the accumulation of drugs and prolong their tumor retention time,providing a feasible strategy for realizing the delivery of small-molecule hydrophobic drugs and tumor PDT.展开更多
Photodynamic therapy(PDT)not only directly eradicates tumor cells but also boosts immunogenicity,promoting antigen presentation and immune cell infiltration.However,the robust antioxidant defense mechanisms within tum...Photodynamic therapy(PDT)not only directly eradicates tumor cells but also boosts immunogenicity,promoting antigen presentation and immune cell infiltration.However,the robust antioxidant defense mechanisms within tumor cells significantly weaken the efficacy of photodynamic immunotherapy.Herein,a supramolecular hybrid nanoassembly is constructed by exploring the synergistic effects of the photodynamic photosensitizer(pyropheophorbide a,PPa)and the ferroptosis inducer(erastin).The erastinmediated inhibition of system X_(c)−significantly downregulates glutathione(GSH)expression,amplifying intracellular oxidative stress,leading to pronounced cell apoptosis,and promoting the release of damageassociated molecular patterns(DAMPs).Additionally,the precise cooperation of PPa and erastin enhances ferroptosis efficiency,exacerbating the accumulation of lipid peroxides(LPOs).Ultimately,LPOs serve as a“find me”signal,while DMAPs act as an“eat me”signal,collectively promoting dendritic cell maturation,enhancing infiltration of the cytotoxic T lymphocytes,and eliciting a robust immune response.This study opens new horizons for enhancing tumor immunotherapy through simultaneous ferroptosis-PDT.展开更多
Cerenkov radiation(CR)can serve as a source of internal light to overcome the limited tissue penetration of external light in conventional photodynamic therapy(PDT).However,insufficient luminescence intensity hinders ...Cerenkov radiation(CR)can serve as a source of internal light to overcome the limited tissue penetration of external light in conventional photodynamic therapy(PDT).However,insufficient luminescence intensity hinders the clinical application of CR-PDT.Here,we developed a glutathione-responsive biomimetic nanoplatform by fusing cancer cell membranes and liposomes loaded with photosensitizer hematoporphyrin monomethyl ether(HMME)and a radiation energy amplifier Eu^(3+),named HMME-Eu@LEV.Colloidal Eu^(3+)convertsγ-radiation and CR from radioisotopes into fluorescence to enhance antitumor effects.Sequential administration ensures co-localization of HMME-Eu@LEV and radiopharmaceutical^(18)F-fluorodeoxyglucose(FDG)at the tumor site,triggering enhanced CR-PDT and immunogenic cell death.Our observations indicated that luminescence resonance energy transfer between Eu^(3+)and HMME was efficient,and Cerenkov luminescence from Eu@LEV+FDG was approximately 5.6-fold higher in intensity than that from FDG alone.As a result,abundant ROS were generated,and macrophages in the tumor microenvironment were polarized from M2 to M1.In addition,the immunosuppressive tumor microenvironment could be reversed by promoting the maturation of dendritic cells and infiltration of cytotoxic T lymphocytes.The activated immune system effectively inhibited the growth of primary tumors and spread of distant metastases.Our work demonstrates the feasibility of CR-PDT without an external light source and the critical role of nanomaterials in personalized medicine.展开更多
Photodynamic therapy(PDT)has emerged as a promising approach for tumor treatment due to its noninvasiveness and high selectivity.However,the off-target activation of phototoxicity and the limited availability of tumor...Photodynamic therapy(PDT)has emerged as a promising approach for tumor treatment due to its noninvasiveness and high selectivity.However,the off-target activation of phototoxicity and the limited availability of tumor-specific biomarkers pose challenges for effective PDT.Here,we present the development of a novel ratiometric near-infrared-II(NIR-II)fluorescent organic nanoprobe,BTz-IC@IR1061,which responds specifically to hypochlorite(HClO)within tumors.This nanoprobe allows ratiometric fluorescence imaging to monitor and guide activated tumor PDT.BTz-IC@IR1061 nanoparticles were synthesized by codoping the small molecule dye BTz-IC,which generates reactive oxygen species(ROS),with the commercial dye IR1061.The presence of HClO selectively activates the fluorescence and photodynamic properties of BTz-IC while destroying IR1061,enabling controlled release of ROS for tumor therapy.We demonstrated the high selectivity of the nanoprobe for HClO,as well as its excellent photostability,photoacoustic imaging capability,and photothermal effects.Furthermore,in vivo studies revealed effective tumor targeting and remarkable tumor growth inhibition through tumor-activated PDT.Our findings highlight the potential of BTz-IC@IR1061 as a promising tool for tumor-specific PDT,providing new opportunities for precise and controlled cancer therapy.展开更多
Innovative anti-cancer therapies that activate the immune system show promise in combating cancers resistant to conventional treatments.Photodynamic therapy(PDT)is one such treatment,which not only directly eliminates...Innovative anti-cancer therapies that activate the immune system show promise in combating cancers resistant to conventional treatments.Photodynamic therapy(PDT)is one such treatment,which not only directly eliminates tumor cells but also functions as an in situ tumor vaccine by enhancing tumor immunogenicity and triggering anti-tumor immune responses through immunogenic cell death(ICD).However,the effectiveness of PDT in enhancing immune responses is influenced by factors,such as photosensitizers and the tumor microenvironment,particularly hypoxia.Current clinically used PDT heavily relies on oxygen(O_(2))availability and can be limited by tumor hypoxia.Additionally,the tumor immunosuppressive microenvironment induced by hypoxia affects the anti-tumor immunity of tumor-infiltrating effector T cells.Meanwhile,the immunosuppressive myeloid-lineage cells are recruited to the hypoxic tumor tissue and exhibit higher immunosuppressive capabilities under hypoxia conditions.Consequently,numerous strategies have been developed to modulate tumor hypoxia or to create hypoxia-compatible PDT,aiming to reduce the effects of tumor hypoxia on PDT-driven immunotherapy.This review investigates these strategies,including approaches to alleviate,exploit,and disregard tumor hypoxia within the context of PDT/immunotherapy.It also emphasizes the role of advanced nanomedicine and its benefits in these strategies,while outlining current challenges and future prospects in the field.展开更多
Photodynamic therapy (PDT) is undoubtedly a cutting-edge strategy for precise tumor therapy because of its unprecedented superiorities, such as negligible long-lasting adverse effects, high spatial and temporal select...Photodynamic therapy (PDT) is undoubtedly a cutting-edge strategy for precise tumor therapy because of its unprecedented superiorities, such as negligible long-lasting adverse effects, high spatial and temporal selectivity, and inappreciable drug resistance. While the operation wavelengths of the commonly used photosensitizers (PSs) are located in visible or first near-infrared (NIR-I, 650–900 nm) region. The lights in these regions possess relatively low penetration depth, which makes PDT unsuitable for deep-tissue treatment. Near-infrared-II (NIR-II, 1000–1700 nm) light with high tissue penetration ability can be employed as excitation source for PDT, which provides a promising alternative for precision therapy of deep-seated tumors. However, designing NIR-II activated PSs is in its infancy, and still faces many challenges, such as severe nonradiative relaxation and difficulties in adjusting energy levels. This paper reviews the therapeutic mechanisms of PDT and recent strategies for designing NIR-II activated inorganic PSs. The inorganic NIR-II PSs are classified based on their functions (such as type II PSs, type I PSs, and PSs with specific properties), and their applications for effective and precision deep-tissue treatment are summarized comprehensively. Furthermore, the major issues of applying these PSs in clinical practices are also discussed.展开更多
Bacterial infections pose a significant threat to human health and entail substantial economic losses.Due to the broad-spectrum antibacterial effect and low susceptibility to drug resistance,photodynamic therapy(PDT),...Bacterial infections pose a significant threat to human health and entail substantial economic losses.Due to the broad-spectrum antibacterial effect and low susceptibility to drug resistance,photodynamic therapy(PDT),a nontraditional antibacterial approach,has garnered a lot of attention.In PDT,the selection of photosensitizer(PS)is crucial because it directly affects the efficiency and safety of the treatment.As a versatile fluorophore,the advantages of 4,4-difluoro-4-bora-3a,4a-diaza-s-indacene(BODIPY)used as a PS for antibacterial PDT are mainly reflected in its high quantum yield of singlet oxygen,easy modification,and exceptional photostability.Through strategic chemical modifications of the BODIPY structures,it is possible to enhance their photodynamic antibacterial activity and refine their selectivity for bacterial killing.This review focuses on the application of BODIPY-based PSs for treating bacterial infections.According to the design strategies of photodynamic antibacterial materials incorporating BODIPY,a variety of representative therapeutic agents having emerged in recent years are classified and discussed,aiming to offer insights for future research and development in this field.展开更多
Photodynamic therapy(PDT)is widely used in cancer treatment because of its noninvasiveness and minimal side effects.However,low therapeutic efficiency and the challenge of treatment visualization limit its development...Photodynamic therapy(PDT)is widely used in cancer treatment because of its noninvasiveness and minimal side effects.However,low therapeutic efficiency and the challenge of treatment visualization limit its development.Herein,we constructed a simple yet efficient lanthanide-doped theranostic nanoplatform termed as LiLuF_(4):Yb,Er,Ce@LiYF_(4)@LiLuF_(4):Nd-chlorine 6(TNPs-Ce6)that enables real-time monitoring of the therapeutic effects of PDT.Upon orthogonal excitation by near-infrared(NIR)light,the Nd^(3+)-doped TNPs activated the triplets of Ce6 photosensitizers via a direct lanthanide-triplet energy transfer process,which allowed to directly active the low-lying triplet state of the photosensitizer without undergoing singlet-triplet intersystem crossing(ISC)process,thereby significantly enhancing the efficiency of the photodynamic process.Meanwhile,the incorporation of Er^(3+)ions within the core endowed the nanoplatform with NIR-Ⅱb imaging capabilities,allowing convenient real-time monitoring of the photodynamic treatment process.Characterization tests revealed that the TNPs-Ce6 nanoplatform,exhibiting an NIR quantum yield of 21.7%at an ultralow excitation power density of 0.1 W cm^(-2),provides a real-time imaging resolution as low as75μm in the NIR-Ⅱb range and achieves a tumor suppression rate of 94%.Therefore,this highly efficient theranostic nanoplatform,with real-time treatment monitoring capability,demonstrates significant potential in cancer therapy.展开更多
Magnesium implants have received widespread attention in orthopaedic surgery.However,the mechanical degradation and concurrent inflammation caused by the rapid corrosion of Mg limits their applications.In this study,a...Magnesium implants have received widespread attention in orthopaedic surgery.However,the mechanical degradation and concurrent inflammation caused by the rapid corrosion of Mg limits their applications.In this study,a kind of unique core-shell heterojunction CuS@PPy nanostructures was synthesized and then incorporated in polycaprolactone(PCL)to construct an intelligent coating(CuS@PPy/PCL)on micro-arc-oxidized Mg implants.The PCL-based coating can realize near-infrared(NIR)-driven antibacterial and controllable Mg dissolution according to different bone healing stages.At the beginning of bone remodelling,the coating exhibits promising antibacterial properties with 99.67%and 99.17%efficacy against S.aureus and E.coli,respectively,thanks to the singlet oxygen(^(1)O_(2))and alkoxyl radicals(RO·)generated by the photodynamic effect of CuS@PPy heterojunction under low-power NIR light(1.5 W/cm^(2)).In the bone reparative stage,the PCL-based coating can maintain high corrosion resistance to meet the mechanical requirements of Mg implants in human body fluid.However,after the complete rehabilitation of bones,through a high-power(2 W/cm^(2))NIR light,the PCL-based coating changed from an elastic to a viscous flow state(44.7℃)under the photothermal effects of CuS@PPy,leading to quick degradation of the PCL-based coating and following accelerating dissolution of the Mg implant(avoiding secondary surgery).Hopefully,this NIR-responsive coating may provide an innovative method for the antibacterial and controllable dissolution of Mg implants.展开更多
Integrating multiple modalities of cancer therapies for synergistic and enhanced therapeutic efficacy remains challenging.Herein,flash nanoprecipitation(FNP),a kinetically driven process,was employed to expedite the c...Integrating multiple modalities of cancer therapies for synergistic and enhanced therapeutic efficacy remains challenging.Herein,flash nanoprecipitation(FNP),a kinetically driven process,was employed to expedite the coordination reaction time required for nano-encapsulate components with completely opposite physiochemical properties including sorafenib(SRF),hemoglobin(Hb),chlorin e6(Ce6),and indocyanine green(ICG)into a multi-component HSCI nanomedicine.Hydrophilic components Hb and ICG interact to form hydrophobic ICG-Hb complexes under electrostatic and hydrophobic interactions.This process facilitates the characteristic time of nucleation(τ_(nucleation))to match the characteristic mixing time(τ_(mix))of the FNP process,resulting in the formulation of kinetically stable nanomedicine,overcoming the long equilibrium times and instability issues associated with thermodynamic assembly.Importantly,pH-responsive structure is also easily but effectively integrated in nanomedicine during this kinetically driven formulation to manipulate its structures.In the acidic tumor microenvironment(TME),the pH-stimulated morphology transformation of HSCI nanomedicine boosts its reactive oxygen species(ROS)generation efficiency and photothermal efficacy,endowing it with better antitumor suppression.In vitro and in vivo experiments reveal that the HSCI nanomedicine offers a synergistic therapeutic effect and stronger tumor suppression compared with single therapies.These results open a new window for developing strategies for multimodal combinatory cancer therapies.展开更多
Tetra-aminophenyl porphyrin(TAPP)-grafted Zn-Ag-In-S quantum dots(ZAIS QDs)/poly(maleic anhydride-alt-1-octadecene)(PMAO)nanoparticles were synthesized and their photoluminescence properties as well as photodynamic pr...Tetra-aminophenyl porphyrin(TAPP)-grafted Zn-Ag-In-S quantum dots(ZAIS QDs)/poly(maleic anhydride-alt-1-octadecene)(PMAO)nanoparticles were synthesized and their photoluminescence properties as well as photodynamic properties were studied.ZAIS QDs showed the brightest photoluminescence and highest quantum yield at an optimized Zn feeding molar ratio of 20%.Those TAPP-grafted nanoparticles(i.e.,ZAIS/PMAO-g-TAPP)were able to produce ^(1)O_(2) in aqueous solution under light irradiation as indicated by the ^(1)O_(2) indicator,9,10-anthracenediyl-bis(methylene)dimalonic acid(ADMA).ZAIS/PMAO-g-TAPP nanoparticles also demonstrate good biocompatibility and low dark toxicity even at a concentration as high as 2.8 mg·mL^(−1),whith can be applied as both a fluorescence probe and a photodynamic therapy(PDT)agent.The PDT treatment showed that the viability of melanoma A2058 cells was less than 10%after treatment with the 420 nm light irradiation for 15 min at a photosensitizer concentration of 1.7 mg·mL^(−1).During the PDT treatment with Escherichia coli,the survival rate of the bacteria decreased by~95%after light irradiation at the same concentration.Such dual-functional ZAIS/PMAO-g-TAPP nanoparticles researched in this study demonstrate promising potential for fluorescence labeling as well as effective PDT treatment against cancer cells and bacteria.展开更多
Photodynamic therapy(PDT)is an emerging minimally invasive therapeutic modality that relies on the activation of a photosensitizing agent by light of a specific wavelength in the presence of molecular oxygen,leading t...Photodynamic therapy(PDT)is an emerging minimally invasive therapeutic modality that relies on the activation of a photosensitizing agent by light of a specific wavelength in the presence of molecular oxygen,leading to the generation of reactive oxygen species(ROS).This mechanism facilitates selective cytotoxic effects within pathological tissues and has demonstrated therapeutic potential across diverse disease contexts.However,the broader clinical applications remain limited by photosensitizer selectivity,shallow light penetration,and the risk of off-target cytotoxicity.Recent advancements in PDT have focused on the development of next-generation photosensitizers,the integration of nanotechnology for enhanced delivery and targeting,and the strategic combination of PDT with complementary therapeutic approaches.Experimental animal models play a crucial role in validating the efficacy and safety of PDT,optimizing its therapeutic parameters,and determining its mechanisms of action.This review provides a comprehensive overview of PDT applications in various disease models,including oncological,infectious,and nonconventional indications.Special emphasis is placed on the importance of large animal models in PDT research,such as rabbits,pigs,dogs,and non-human primates,which provide experimental platforms that more closely resemble human physiological and pathological states.The use of these models for understanding the mechanisms of PDT,optimizing therapeutic regimens,and evaluating clinical outcomes is also discussed.This review aims to inform future directions in PDT research and emphasizes the importance of selecting appropriate preclinical animal models to facilitate successful clinical translation.展开更多
An increasing number of studies have focused on depleting lactate and modulating the tumor’s lactic microenvironment to interfere with tumor progression,particularly in breast cancer.Lactate accumulation in tumors co...An increasing number of studies have focused on depleting lactate and modulating the tumor’s lactic microenvironment to interfere with tumor progression,particularly in breast cancer.Lactate accumulation in tumors contributes to a highly acidic microenvironment that promotes cancer cell survival and resistance to therapies.However,existing lactate depletion agents,primarily enzymes and macromolecules,fall short of clinical applications due to poor stability and their ability to only perform solitary lactate depletion without interfering with the transport process.Consequently,the development of stable molecules that deplete lactate and interfere with lactate transport is critically needed.Therefore,in this study,chlorin e6(Ce6)-gadolinium chloride(GdCl_(3))-flavin adenine dinucleotide(FAD)/tamoxifen(TAM)molecular chelates were prepared.The chelates fully interfered with lactate transport,depleted lactate in the tumor microenvironment,mitigated photodynamic therapy resistance,and realized synergistic photodynamic-hormonal therapy.FAD has promising capabilities in regulating lactate levels and mitigating acidic microenvironments.However,a strategy for depleting lactate by chelating the coenzyme FAD to form nanoparticles has not yet been reported.Tamoxifen disrupts tumor development and interferes with lactate transport by binding to estrogen receptor and inhibiting the expression of monocarboxylate transporter.In addition,coupling with Gd^(3+)increased the solubility of Ce6,thereby improving the photodynamic therapy effectiveness.This innovative strategy improves therapeutic efficacy and offers a promising approach for breast cancer treatment.展开更多
Photodynamic therapy(PDT)presents a promising avenue in cancer treatment.Erlotinib,an FDAapproved anticancer drug targeting epidermal growth factor receptor(EGFR),has shown effectiveness in normalizing tumor vasculatu...Photodynamic therapy(PDT)presents a promising avenue in cancer treatment.Erlotinib,an FDAapproved anticancer drug targeting epidermal growth factor receptor(EGFR),has shown effectiveness in normalizing tumor vasculature across various tumors,thereby promoting tumor oxygenation and facilitating PDT.In this work,erlotinib was conjugated with a near-infrared(NIR)photosensitizer,benzo[a]phenoselenazinium,yielding three EGFR-targeted PDT agents(NBSe-n C-Er).These newly synthesized photosensitizers demonstrate specificity in binding to EGFR,thereby enhancing their accumulation in cancer cells and tumors,and consequently improving the efficiency of both PDT and chemotherapy.Additionally,the NIR fluorescence emitted by the photosensitizer allows for imaging-guided therapy,offering a non-invasive means of monitoring treatment progress.The distinctive properties of the three-inone photosensitizer render it an ideal candidate for precise tumor treatment,overcoming the limitations of conventional therapies.展开更多
The natural curcumin-mediated photodynamic inactivation(PDI)was developed,and its inactivation potency against Fusarium graminearum in vitro and in vivo was systematically investigated by fluorescence probe assay,tryp...The natural curcumin-mediated photodynamic inactivation(PDI)was developed,and its inactivation potency against Fusarium graminearum in vitro and in vivo was systematically investigated by fluorescence probe assay,trypan blue staining,scanning electron microscope(SEM),confocal laser scanning microscopy(CLSM),etc.Results showed that under the irradiation of blue LED,the photosensitizer of curcumin was excited to generate massive reactive oxygen species(ROS)in the cells of F.graminearum,and the PDI completely inactivated their mycelia and spores under the treatment of 150μM curcumin and 10.8 J/cm^(2)irradiation.Further analysis found that the PDI ruptured the cellular microstructures,damaged the cell membrane by increasing its permeability and oxidizing the lipids,degraded the intracellular DNA and proteins inside the spores of F.graminearum.Meanwhile,the PDI also potently killed>99.99%spores of F.graminearum on maize under the treatment of 200μM curcumin and 10.8 J/cm^(2)irradiation.Moreover,the PDI suppressed the production of zearalenone(ZEN),and residual ZEN could not be detected after the storage of maize for 10 days.Therefore,this study systematically explored the inactivation efficiency of curcumin-mediated PDI against both the mycelia and spores of F.graminearum,which provides a valid and promising method to control the fungal hazards in grains.展开更多
Photodynamic therapy(PDT)has emerged as a promising protocol for cancer therapy.However,real-time monitoring of PDT progress and accurate determination of the optimal treatment timing remain challenges.In this work,we...Photodynamic therapy(PDT)has emerged as a promising protocol for cancer therapy.However,real-time monitoring of PDT progress and accurate determination of the optimal treatment timing remain challenges.In this work,we selected carbon dots(CDs)and new indocyanine green(IR820)as building units to fabricate a smart nanotheranostics(CDs-IR820 assembly)with the characteristics of controlled release and real-time imaging to solve the time gap between diagnosis and treatment.The fabricated CDs-IR820 assembly locked the photosensitivity of the CDs and could degrade under 750 nm laser irradiation to achieve controlled release of the CDs,thus used for cell imaging and producing single oxygen under the white light.Besides,the released CDs could migrate from the mitochondria to the nucleus during the PDT process,indicating the cell activity,which facilitated the regulation of treatment parameters to achieve the precise PDT for cancer.展开更多
The efficacy of photodynamic therapy(PDT)for breast tumors is hindered by challenges such as inadequate tumor targeting,limited treatment depth,and strong oxygen dependence.Herein,a promising photosensitizer VP-B was ...The efficacy of photodynamic therapy(PDT)for breast tumors is hindered by challenges such as inadequate tumor targeting,limited treatment depth,and strong oxygen dependence.Herein,a promising photosensitizer VP-B was developed to simultaneously address all the aforementioned issues for the treatment of hypoxic deep-seated breast tumors.The biotinylated photosensitizer VP-B not only exhibited precise targeting towards breast tumor tissue,but also efficiently triggered the generation of abundant1O2and O2-·under 690 nm red light irradiation.Indeed,the red light penetration ability enabled VP-B to achieve successful application in a mouse orthotopic breast tumor model.After intravenous administration,VP-B can selectively target tumor tissues and significantly inhibit the growth of hypoxic deep-seated tumors.Therefore,this new typeⅠ&Ⅱphotosensitizer could boost fluorescence-guided photodynamic therapy of other hypoxic solid tumors.展开更多
Diseases associated with bacterial infection,especially those caused by gram-negative bacteria,have been posing a serious threat to human health.Photodynamic therapy based on aggregation-induced emission(AIE)photosens...Diseases associated with bacterial infection,especially those caused by gram-negative bacteria,have been posing a serious threat to human health.Photodynamic therapy based on aggregation-induced emission(AIE)photosensitizer have recently emerged and provided a promising approach for bacterial discrimination and efficient photodynamic antimicrobial applications.However,they often suffer from the shorter excitation wavelength and lower molar extinction coefficients in the visible region,severely limiting their further applications.Herein,three novel BF_(2)-curcuminoid-based AIE photosensitizers,TBBC,TBC and TBBC-C8,have been rationally designed and successfully developed,in which OCH_(3)-and OC_(8)H_(17)-substituted tetraphenylethene(TPE)groups serve as both electron donor(D)and AIE active moieties,BF_(2)bdk group functions as electron acceptor(A),and styrene(or ethylene)group asπ-bridge in this D-π-A-π-D system,respectively.As expected,these resulting BF_(2)-curcuminoids presented solvent-dependent photophysical properties with large molar extinction coefficients in solutions and excellent AIE properties.Notably,TBBC showed an effective singlet oxygen generation efficiency thanks to the smaller singlet-triplet energy gap(△E_(ST)),and remarkable photostability under green light exposure at 530nm(8.9 mW/cm^(2)).More importantly,TBBC was demonstrated effectiveness in selective staining and photodynamic killing of Escherichia coli(E.coli)in vitro probably due to its optimal molecular size compared with TBC and TBBC-C8.Therefore,TBBC will have great potential as a novel AIE photosensitizer to apply in the discrimination and selective sterilization between Gram-positive and Gram-negative bacteria.展开更多
The complexity of cancer therapy has led to the emergence of combination therapy as a promising approach to enhance treatment efficacy and safety.The integration of glutathione(GSH)-activatable two-photon photodynamic...The complexity of cancer therapy has led to the emergence of combination therapy as a promising approach to enhance treatment efficacy and safety.The integration of glutathione(GSH)-activatable two-photon photodynamic therapy(TP-PDT)and chemodynamic therapy(CDT)offers the possibility to advance precision and efficacy in anti-cancer treatments.In this study,a GSH-activatable photosensitizer(PS),namely copper-elsinochrome(CuEC),is synthesized and utilized for combination second nearinfrared(NIR-II)TP-PDT/CDT.The Cu^(2+)acts as a“lock”,suppressing the fluorescence and^(1)O_(2)generation ability of EC in a normal physiological environment(“OFF”state).However,the overexpressed GSH in the tumor microenvironment acts as the“key”,resulting in the release of EC(“ON”state)and Cu^(+)(reduced by GSH).The released EC can be utilized for fluorescence imaging and TP-PDT under NIR-II(λ=1000 nm)two-photon excitation,while Cu+can generate highly toxic hydroxyl radicals(•OH)via Fenton-like reaction for CDT.Additionally,this process consumes GSH and diminishes the tumor’s antioxidant capacity,thereby augmenting the efficacy of combination therapy.The CuEC achieves significant tumor cell ablation in both 2D monolayer cells and 3D multicellular tumor spheres through the combination of NIR-II TP-PDT and CDT.展开更多
Basal cell carcinoma(BCC)and cutaneous squamous cell carcinoma(cSCC),as certain forms of nonmelanoma skin cancer(NMSC)or keratinocyte carcinoma,are the most common forms of malignant neoplasms worldwide(Sharp et al.,2...Basal cell carcinoma(BCC)and cutaneous squamous cell carcinoma(cSCC),as certain forms of nonmelanoma skin cancer(NMSC)or keratinocyte carcinoma,are the most common forms of malignant neoplasms worldwide(Sharp et al.,2024).BCC and cSCC have been identified as two major components of NMSC,comprising one-third of all malignancies(Burton et al.,2016).Generally speaking,patients with NMSC tend to have relatively favorable survival outcomes,while different histopathological subtypes of NMSC exhibit distinct biological behaviors(Stătescu et al.,2023).展开更多
文摘A nanomicelle(denoted as TPGS/Ppa)was fabricated via the coassembly of the amphiphilic D-α-tocopheryl polyethylene glycol 1000 succinate(TPGS)and the hydrophobic photosensitizer pyropheophorbide a(Ppa)for photodynamic therapy(PDT).The obtained nanomicelle possessed a spherical structure with a diameter of(18.0±2.2)nm and a zeta potential of approximately -18 mV.Besides,the nanomicelle exhibited excellent photostability,biocompatibility,and phototoxicity,and could effectively reach the tumor region via the enhanced permeability and retention effect.Additionally,it could be found that the TPGS/Ppa nanomicelle exhibited higher phototoxicity against 4T1 murine mammary cancer cells than free Ppa.In the 4T1 tumor-bearing mouse model,the nanomicelle showed an excellent antitumor therapeutic effect.This study develops a new type of photodynamic nanomicelle TPGS/Ppa,which can increase the accumulation of drugs and prolong their tumor retention time,providing a feasible strategy for realizing the delivery of small-molecule hydrophobic drugs and tumor PDT.
基金financially supported by the National Natural Science Foundation of China(No.82161138029)the Basic Research Projects of Liaoning Provincial Department of Education(No.LJKZZ20220109)the Shenyang Youth Science and Technology Innovation Talents Program(No.RC210452).
文摘Photodynamic therapy(PDT)not only directly eradicates tumor cells but also boosts immunogenicity,promoting antigen presentation and immune cell infiltration.However,the robust antioxidant defense mechanisms within tumor cells significantly weaken the efficacy of photodynamic immunotherapy.Herein,a supramolecular hybrid nanoassembly is constructed by exploring the synergistic effects of the photodynamic photosensitizer(pyropheophorbide a,PPa)and the ferroptosis inducer(erastin).The erastinmediated inhibition of system X_(c)−significantly downregulates glutathione(GSH)expression,amplifying intracellular oxidative stress,leading to pronounced cell apoptosis,and promoting the release of damageassociated molecular patterns(DAMPs).Additionally,the precise cooperation of PPa and erastin enhances ferroptosis efficiency,exacerbating the accumulation of lipid peroxides(LPOs).Ultimately,LPOs serve as a“find me”signal,while DMAPs act as an“eat me”signal,collectively promoting dendritic cell maturation,enhancing infiltration of the cytotoxic T lymphocytes,and eliciting a robust immune response.This study opens new horizons for enhancing tumor immunotherapy through simultaneous ferroptosis-PDT.
基金supported by the Major Science and Technology Special Projects in Henan Province(No.221100310100)co-construction Project of Henan Medical Science and Technology(LHGJ20230286).
文摘Cerenkov radiation(CR)can serve as a source of internal light to overcome the limited tissue penetration of external light in conventional photodynamic therapy(PDT).However,insufficient luminescence intensity hinders the clinical application of CR-PDT.Here,we developed a glutathione-responsive biomimetic nanoplatform by fusing cancer cell membranes and liposomes loaded with photosensitizer hematoporphyrin monomethyl ether(HMME)and a radiation energy amplifier Eu^(3+),named HMME-Eu@LEV.Colloidal Eu^(3+)convertsγ-radiation and CR from radioisotopes into fluorescence to enhance antitumor effects.Sequential administration ensures co-localization of HMME-Eu@LEV and radiopharmaceutical^(18)F-fluorodeoxyglucose(FDG)at the tumor site,triggering enhanced CR-PDT and immunogenic cell death.Our observations indicated that luminescence resonance energy transfer between Eu^(3+)and HMME was efficient,and Cerenkov luminescence from Eu@LEV+FDG was approximately 5.6-fold higher in intensity than that from FDG alone.As a result,abundant ROS were generated,and macrophages in the tumor microenvironment were polarized from M2 to M1.In addition,the immunosuppressive tumor microenvironment could be reversed by promoting the maturation of dendritic cells and infiltration of cytotoxic T lymphocytes.The activated immune system effectively inhibited the growth of primary tumors and spread of distant metastases.Our work demonstrates the feasibility of CR-PDT without an external light source and the critical role of nanomaterials in personalized medicine.
基金supported by the National Natural Science Foundation of China(Nos.22374040,U21A20287,21974039,21890744)the Key Projects of National Natural Science Foundation of China(No.22234003)+1 种基金the National Key R&D Program of China(No.2019YFA0210100)the Fundamental Research Funds for the Central Universities.
文摘Photodynamic therapy(PDT)has emerged as a promising approach for tumor treatment due to its noninvasiveness and high selectivity.However,the off-target activation of phototoxicity and the limited availability of tumor-specific biomarkers pose challenges for effective PDT.Here,we present the development of a novel ratiometric near-infrared-II(NIR-II)fluorescent organic nanoprobe,BTz-IC@IR1061,which responds specifically to hypochlorite(HClO)within tumors.This nanoprobe allows ratiometric fluorescence imaging to monitor and guide activated tumor PDT.BTz-IC@IR1061 nanoparticles were synthesized by codoping the small molecule dye BTz-IC,which generates reactive oxygen species(ROS),with the commercial dye IR1061.The presence of HClO selectively activates the fluorescence and photodynamic properties of BTz-IC while destroying IR1061,enabling controlled release of ROS for tumor therapy.We demonstrated the high selectivity of the nanoprobe for HClO,as well as its excellent photostability,photoacoustic imaging capability,and photothermal effects.Furthermore,in vivo studies revealed effective tumor targeting and remarkable tumor growth inhibition through tumor-activated PDT.Our findings highlight the potential of BTz-IC@IR1061 as a promising tool for tumor-specific PDT,providing new opportunities for precise and controlled cancer therapy.
基金supported by the Qin Chuangyuan Traditional Chinese Medicine(TCM)and Innovation Research and Development Project of Shaanxi Provincial Administration of TCM(No.2022-QCYZH-017)Natural Science Foundation of Zhejiang Province(No.LY24E030010)+5 种基金Natural Science Foundation of Shaanxi Province(Nos.2022JM183,2024JC-YBMS-272)the Shaanxi Fundamental Science Research Project for Chemistry&Biology(No.22JHQ072)Shaanxi Provincial Key R&D Program(No.2022SF-342HZ)the Fundamental Research Funds for the Central Universities(Nos.xzy012022037,xzy012023002)the Postdoctoral Science Foundation of Shaanxi Province(No.2023BSHYDZZ05)Foundation by Shaanxi Provincial Administration of TCM(No.2021-ZZ-JC032)。
文摘Innovative anti-cancer therapies that activate the immune system show promise in combating cancers resistant to conventional treatments.Photodynamic therapy(PDT)is one such treatment,which not only directly eliminates tumor cells but also functions as an in situ tumor vaccine by enhancing tumor immunogenicity and triggering anti-tumor immune responses through immunogenic cell death(ICD).However,the effectiveness of PDT in enhancing immune responses is influenced by factors,such as photosensitizers and the tumor microenvironment,particularly hypoxia.Current clinically used PDT heavily relies on oxygen(O_(2))availability and can be limited by tumor hypoxia.Additionally,the tumor immunosuppressive microenvironment induced by hypoxia affects the anti-tumor immunity of tumor-infiltrating effector T cells.Meanwhile,the immunosuppressive myeloid-lineage cells are recruited to the hypoxic tumor tissue and exhibit higher immunosuppressive capabilities under hypoxia conditions.Consequently,numerous strategies have been developed to modulate tumor hypoxia or to create hypoxia-compatible PDT,aiming to reduce the effects of tumor hypoxia on PDT-driven immunotherapy.This review investigates these strategies,including approaches to alleviate,exploit,and disregard tumor hypoxia within the context of PDT/immunotherapy.It also emphasizes the role of advanced nanomedicine and its benefits in these strategies,while outlining current challenges and future prospects in the field.
基金supported by the National Natural Science Foundation of China(Nos.22175098,52373142)the Jiangsu Planned Projects for Postdoctoral Research Funds(No.2021K114B)the Huali Talents Program of Nanjing University of Posts and Telecommunications,the Postgraduate Research&Practice Innovation Program of Jiangsu Province(No.KYCX23_0984)。
文摘Photodynamic therapy (PDT) is undoubtedly a cutting-edge strategy for precise tumor therapy because of its unprecedented superiorities, such as negligible long-lasting adverse effects, high spatial and temporal selectivity, and inappreciable drug resistance. While the operation wavelengths of the commonly used photosensitizers (PSs) are located in visible or first near-infrared (NIR-I, 650–900 nm) region. The lights in these regions possess relatively low penetration depth, which makes PDT unsuitable for deep-tissue treatment. Near-infrared-II (NIR-II, 1000–1700 nm) light with high tissue penetration ability can be employed as excitation source for PDT, which provides a promising alternative for precision therapy of deep-seated tumors. However, designing NIR-II activated PSs is in its infancy, and still faces many challenges, such as severe nonradiative relaxation and difficulties in adjusting energy levels. This paper reviews the therapeutic mechanisms of PDT and recent strategies for designing NIR-II activated inorganic PSs. The inorganic NIR-II PSs are classified based on their functions (such as type II PSs, type I PSs, and PSs with specific properties), and their applications for effective and precision deep-tissue treatment are summarized comprehensively. Furthermore, the major issues of applying these PSs in clinical practices are also discussed.
文摘Bacterial infections pose a significant threat to human health and entail substantial economic losses.Due to the broad-spectrum antibacterial effect and low susceptibility to drug resistance,photodynamic therapy(PDT),a nontraditional antibacterial approach,has garnered a lot of attention.In PDT,the selection of photosensitizer(PS)is crucial because it directly affects the efficiency and safety of the treatment.As a versatile fluorophore,the advantages of 4,4-difluoro-4-bora-3a,4a-diaza-s-indacene(BODIPY)used as a PS for antibacterial PDT are mainly reflected in its high quantum yield of singlet oxygen,easy modification,and exceptional photostability.Through strategic chemical modifications of the BODIPY structures,it is possible to enhance their photodynamic antibacterial activity and refine their selectivity for bacterial killing.This review focuses on the application of BODIPY-based PSs for treating bacterial infections.According to the design strategies of photodynamic antibacterial materials incorporating BODIPY,a variety of representative therapeutic agents having emerged in recent years are classified and discussed,aiming to offer insights for future research and development in this field.
基金supported by the Major Research plan of the National Natural Science Foundation of China(No.92361202)National Natural Science Foundation of China(No.12204481)+3 种基金Fund of Fujian Science&Technology Innovation Laboratory for Optoelectronic Information(No.2020ZZ114)Natural Science Foundation of Fujian Province(Nos.2022J05102 and 2024J09062)National Key Research and Development Program of China(Nos.2022YFB3503700 and 2023YFF0713605)Self-deployment Project Research Program of Haixi Institutes,Chinese Academy of Sciences(No.CXZX-2022-GS01)
文摘Photodynamic therapy(PDT)is widely used in cancer treatment because of its noninvasiveness and minimal side effects.However,low therapeutic efficiency and the challenge of treatment visualization limit its development.Herein,we constructed a simple yet efficient lanthanide-doped theranostic nanoplatform termed as LiLuF_(4):Yb,Er,Ce@LiYF_(4)@LiLuF_(4):Nd-chlorine 6(TNPs-Ce6)that enables real-time monitoring of the therapeutic effects of PDT.Upon orthogonal excitation by near-infrared(NIR)light,the Nd^(3+)-doped TNPs activated the triplets of Ce6 photosensitizers via a direct lanthanide-triplet energy transfer process,which allowed to directly active the low-lying triplet state of the photosensitizer without undergoing singlet-triplet intersystem crossing(ISC)process,thereby significantly enhancing the efficiency of the photodynamic process.Meanwhile,the incorporation of Er^(3+)ions within the core endowed the nanoplatform with NIR-Ⅱb imaging capabilities,allowing convenient real-time monitoring of the photodynamic treatment process.Characterization tests revealed that the TNPs-Ce6 nanoplatform,exhibiting an NIR quantum yield of 21.7%at an ultralow excitation power density of 0.1 W cm^(-2),provides a real-time imaging resolution as low as75μm in the NIR-Ⅱb range and achieves a tumor suppression rate of 94%.Therefore,this highly efficient theranostic nanoplatform,with real-time treatment monitoring capability,demonstrates significant potential in cancer therapy.
基金support to this work:the National Natural Science Foundation of China(grant No.50971064,No.51361004)the Innovative Foundation of HUST(grant 2017KFYXJJ164).
文摘Magnesium implants have received widespread attention in orthopaedic surgery.However,the mechanical degradation and concurrent inflammation caused by the rapid corrosion of Mg limits their applications.In this study,a kind of unique core-shell heterojunction CuS@PPy nanostructures was synthesized and then incorporated in polycaprolactone(PCL)to construct an intelligent coating(CuS@PPy/PCL)on micro-arc-oxidized Mg implants.The PCL-based coating can realize near-infrared(NIR)-driven antibacterial and controllable Mg dissolution according to different bone healing stages.At the beginning of bone remodelling,the coating exhibits promising antibacterial properties with 99.67%and 99.17%efficacy against S.aureus and E.coli,respectively,thanks to the singlet oxygen(^(1)O_(2))and alkoxyl radicals(RO·)generated by the photodynamic effect of CuS@PPy heterojunction under low-power NIR light(1.5 W/cm^(2)).In the bone reparative stage,the PCL-based coating can maintain high corrosion resistance to meet the mechanical requirements of Mg implants in human body fluid.However,after the complete rehabilitation of bones,through a high-power(2 W/cm^(2))NIR light,the PCL-based coating changed from an elastic to a viscous flow state(44.7℃)under the photothermal effects of CuS@PPy,leading to quick degradation of the PCL-based coating and following accelerating dissolution of the Mg implant(avoiding secondary surgery).Hopefully,this NIR-responsive coating may provide an innovative method for the antibacterial and controllable dissolution of Mg implants.
基金supported by the National Natural Science Foundation of China(22378126)National Key Research and Development Program of the International scientific and technological innovation cooperation project among governments(2021YFE0100400)Shanghai Science and Technology Innovation Action Plan(22501100500).
文摘Integrating multiple modalities of cancer therapies for synergistic and enhanced therapeutic efficacy remains challenging.Herein,flash nanoprecipitation(FNP),a kinetically driven process,was employed to expedite the coordination reaction time required for nano-encapsulate components with completely opposite physiochemical properties including sorafenib(SRF),hemoglobin(Hb),chlorin e6(Ce6),and indocyanine green(ICG)into a multi-component HSCI nanomedicine.Hydrophilic components Hb and ICG interact to form hydrophobic ICG-Hb complexes under electrostatic and hydrophobic interactions.This process facilitates the characteristic time of nucleation(τ_(nucleation))to match the characteristic mixing time(τ_(mix))of the FNP process,resulting in the formulation of kinetically stable nanomedicine,overcoming the long equilibrium times and instability issues associated with thermodynamic assembly.Importantly,pH-responsive structure is also easily but effectively integrated in nanomedicine during this kinetically driven formulation to manipulate its structures.In the acidic tumor microenvironment(TME),the pH-stimulated morphology transformation of HSCI nanomedicine boosts its reactive oxygen species(ROS)generation efficiency and photothermal efficacy,endowing it with better antitumor suppression.In vitro and in vivo experiments reveal that the HSCI nanomedicine offers a synergistic therapeutic effect and stronger tumor suppression compared with single therapies.These results open a new window for developing strategies for multimodal combinatory cancer therapies.
基金supported by the Top-Notch Academic Programs Project of Jiangsu Higher Education Institutions(TAPP)the Priority Academic Program Development of Jiangsu Higher Education Institutions(PAPD)the CZ-EdU Joint Laboratory on Biomedical Materials(CZ20190019).
文摘Tetra-aminophenyl porphyrin(TAPP)-grafted Zn-Ag-In-S quantum dots(ZAIS QDs)/poly(maleic anhydride-alt-1-octadecene)(PMAO)nanoparticles were synthesized and their photoluminescence properties as well as photodynamic properties were studied.ZAIS QDs showed the brightest photoluminescence and highest quantum yield at an optimized Zn feeding molar ratio of 20%.Those TAPP-grafted nanoparticles(i.e.,ZAIS/PMAO-g-TAPP)were able to produce ^(1)O_(2) in aqueous solution under light irradiation as indicated by the ^(1)O_(2) indicator,9,10-anthracenediyl-bis(methylene)dimalonic acid(ADMA).ZAIS/PMAO-g-TAPP nanoparticles also demonstrate good biocompatibility and low dark toxicity even at a concentration as high as 2.8 mg·mL^(−1),whith can be applied as both a fluorescence probe and a photodynamic therapy(PDT)agent.The PDT treatment showed that the viability of melanoma A2058 cells was less than 10%after treatment with the 420 nm light irradiation for 15 min at a photosensitizer concentration of 1.7 mg·mL^(−1).During the PDT treatment with Escherichia coli,the survival rate of the bacteria decreased by~95%after light irradiation at the same concentration.Such dual-functional ZAIS/PMAO-g-TAPP nanoparticles researched in this study demonstrate promising potential for fluorescence labeling as well as effective PDT treatment against cancer cells and bacteria.
基金supported by the China Postdoctoral Science Foundation(2024M751098,2024M761134)Jilin Province Development and Reform Commission Program(ZKJCFGW2023015)+1 种基金Wenzhou Science&Technology Bureau Basic Public Welfare Research Program(Y20240006)Jilin University Young Teachers and Students Cross-disciplinary Training Project(2023-JCXK-08)。
文摘Photodynamic therapy(PDT)is an emerging minimally invasive therapeutic modality that relies on the activation of a photosensitizing agent by light of a specific wavelength in the presence of molecular oxygen,leading to the generation of reactive oxygen species(ROS).This mechanism facilitates selective cytotoxic effects within pathological tissues and has demonstrated therapeutic potential across diverse disease contexts.However,the broader clinical applications remain limited by photosensitizer selectivity,shallow light penetration,and the risk of off-target cytotoxicity.Recent advancements in PDT have focused on the development of next-generation photosensitizers,the integration of nanotechnology for enhanced delivery and targeting,and the strategic combination of PDT with complementary therapeutic approaches.Experimental animal models play a crucial role in validating the efficacy and safety of PDT,optimizing its therapeutic parameters,and determining its mechanisms of action.This review provides a comprehensive overview of PDT applications in various disease models,including oncological,infectious,and nonconventional indications.Special emphasis is placed on the importance of large animal models in PDT research,such as rabbits,pigs,dogs,and non-human primates,which provide experimental platforms that more closely resemble human physiological and pathological states.The use of these models for understanding the mechanisms of PDT,optimizing therapeutic regimens,and evaluating clinical outcomes is also discussed.This review aims to inform future directions in PDT research and emphasizes the importance of selecting appropriate preclinical animal models to facilitate successful clinical translation.
基金supported by the National Natural Science Foundation of China(No.82373206)Zhejiang Provincial Natural Science Foundation of China under Grant No LHDMZ24H300002National Key Research and Development Program of China(No.2022YFE0107800,2023YFA1008603).
文摘An increasing number of studies have focused on depleting lactate and modulating the tumor’s lactic microenvironment to interfere with tumor progression,particularly in breast cancer.Lactate accumulation in tumors contributes to a highly acidic microenvironment that promotes cancer cell survival and resistance to therapies.However,existing lactate depletion agents,primarily enzymes and macromolecules,fall short of clinical applications due to poor stability and their ability to only perform solitary lactate depletion without interfering with the transport process.Consequently,the development of stable molecules that deplete lactate and interfere with lactate transport is critically needed.Therefore,in this study,chlorin e6(Ce6)-gadolinium chloride(GdCl_(3))-flavin adenine dinucleotide(FAD)/tamoxifen(TAM)molecular chelates were prepared.The chelates fully interfered with lactate transport,depleted lactate in the tumor microenvironment,mitigated photodynamic therapy resistance,and realized synergistic photodynamic-hormonal therapy.FAD has promising capabilities in regulating lactate levels and mitigating acidic microenvironments.However,a strategy for depleting lactate by chelating the coenzyme FAD to form nanoparticles has not yet been reported.Tamoxifen disrupts tumor development and interferes with lactate transport by binding to estrogen receptor and inhibiting the expression of monocarboxylate transporter.In addition,coupling with Gd^(3+)increased the solubility of Ce6,thereby improving the photodynamic therapy effectiveness.This innovative strategy improves therapeutic efficacy and offers a promising approach for breast cancer treatment.
基金supported by the National Natural Science Foundation of China(Nos.22278447 and 22178395)State Key Laboratory of Fine Chemicals(No.KF2109)State Key Laboratory of Chemo/Biosensing and Chemometrics(No.20230768)。
文摘Photodynamic therapy(PDT)presents a promising avenue in cancer treatment.Erlotinib,an FDAapproved anticancer drug targeting epidermal growth factor receptor(EGFR),has shown effectiveness in normalizing tumor vasculature across various tumors,thereby promoting tumor oxygenation and facilitating PDT.In this work,erlotinib was conjugated with a near-infrared(NIR)photosensitizer,benzo[a]phenoselenazinium,yielding three EGFR-targeted PDT agents(NBSe-n C-Er).These newly synthesized photosensitizers demonstrate specificity in binding to EGFR,thereby enhancing their accumulation in cancer cells and tumors,and consequently improving the efficiency of both PDT and chemotherapy.Additionally,the NIR fluorescence emitted by the photosensitizer allows for imaging-guided therapy,offering a non-invasive means of monitoring treatment progress.The distinctive properties of the three-inone photosensitizer render it an ideal candidate for precise tumor treatment,overcoming the limitations of conventional therapies.
基金supported by the National Key Research and Development Program of China(2022YFE0139500)National Natural Science Foundation of China(32102105)+3 种基金Guangdong Basic and Applied Basic Research Foundation(2024A15150130262023A1515140136)Special Projects in Key Areas of Higher Education Institution in Guangdong Province(2024ZDZX2090)Guangdong Provincial Key Laboratory of Intelligent Food Manufacturing(2022B1212010015)。
文摘The natural curcumin-mediated photodynamic inactivation(PDI)was developed,and its inactivation potency against Fusarium graminearum in vitro and in vivo was systematically investigated by fluorescence probe assay,trypan blue staining,scanning electron microscope(SEM),confocal laser scanning microscopy(CLSM),etc.Results showed that under the irradiation of blue LED,the photosensitizer of curcumin was excited to generate massive reactive oxygen species(ROS)in the cells of F.graminearum,and the PDI completely inactivated their mycelia and spores under the treatment of 150μM curcumin and 10.8 J/cm^(2)irradiation.Further analysis found that the PDI ruptured the cellular microstructures,damaged the cell membrane by increasing its permeability and oxidizing the lipids,degraded the intracellular DNA and proteins inside the spores of F.graminearum.Meanwhile,the PDI also potently killed>99.99%spores of F.graminearum on maize under the treatment of 200μM curcumin and 10.8 J/cm^(2)irradiation.Moreover,the PDI suppressed the production of zearalenone(ZEN),and residual ZEN could not be detected after the storage of maize for 10 days.Therefore,this study systematically explored the inactivation efficiency of curcumin-mediated PDI against both the mycelia and spores of F.graminearum,which provides a valid and promising method to control the fungal hazards in grains.
基金supported by the National Natural Science Foundation of China(Grant No.52272052)the project of the National Key Research and Development Program of China(No.2022YFA1207600).
文摘Photodynamic therapy(PDT)has emerged as a promising protocol for cancer therapy.However,real-time monitoring of PDT progress and accurate determination of the optimal treatment timing remain challenges.In this work,we selected carbon dots(CDs)and new indocyanine green(IR820)as building units to fabricate a smart nanotheranostics(CDs-IR820 assembly)with the characteristics of controlled release and real-time imaging to solve the time gap between diagnosis and treatment.The fabricated CDs-IR820 assembly locked the photosensitivity of the CDs and could degrade under 750 nm laser irradiation to achieve controlled release of the CDs,thus used for cell imaging and producing single oxygen under the white light.Besides,the released CDs could migrate from the mitochondria to the nucleus during the PDT process,indicating the cell activity,which facilitated the regulation of treatment parameters to achieve the precise PDT for cancer.
基金supported financially by the National Key Research and Development Program of China(No.2023YFC3403000)the National Natural Science Foundation of China(No.22378231)the Guangdong Basic and Applied Basic Research Foundation(No.2024A1515012493)。
文摘The efficacy of photodynamic therapy(PDT)for breast tumors is hindered by challenges such as inadequate tumor targeting,limited treatment depth,and strong oxygen dependence.Herein,a promising photosensitizer VP-B was developed to simultaneously address all the aforementioned issues for the treatment of hypoxic deep-seated breast tumors.The biotinylated photosensitizer VP-B not only exhibited precise targeting towards breast tumor tissue,but also efficiently triggered the generation of abundant1O2and O2-·under 690 nm red light irradiation.Indeed,the red light penetration ability enabled VP-B to achieve successful application in a mouse orthotopic breast tumor model.After intravenous administration,VP-B can selectively target tumor tissues and significantly inhibit the growth of hypoxic deep-seated tumors.Therefore,this new typeⅠ&Ⅱphotosensitizer could boost fluorescence-guided photodynamic therapy of other hypoxic solid tumors.
基金National Natural Science Foundation of China(No.32101150)Key Scientific Research Project of Higher Education of Henan Province(No.22A430007)+2 种基金Natural Science Foundation of Henan Province(No.222300420501)the Science and Technology Project of Henan Province(No.242102230119)Innovation and Entrepreneurship Training Program for College students in China(No.202310482001).
文摘Diseases associated with bacterial infection,especially those caused by gram-negative bacteria,have been posing a serious threat to human health.Photodynamic therapy based on aggregation-induced emission(AIE)photosensitizer have recently emerged and provided a promising approach for bacterial discrimination and efficient photodynamic antimicrobial applications.However,they often suffer from the shorter excitation wavelength and lower molar extinction coefficients in the visible region,severely limiting their further applications.Herein,three novel BF_(2)-curcuminoid-based AIE photosensitizers,TBBC,TBC and TBBC-C8,have been rationally designed and successfully developed,in which OCH_(3)-and OC_(8)H_(17)-substituted tetraphenylethene(TPE)groups serve as both electron donor(D)and AIE active moieties,BF_(2)bdk group functions as electron acceptor(A),and styrene(or ethylene)group asπ-bridge in this D-π-A-π-D system,respectively.As expected,these resulting BF_(2)-curcuminoids presented solvent-dependent photophysical properties with large molar extinction coefficients in solutions and excellent AIE properties.Notably,TBBC showed an effective singlet oxygen generation efficiency thanks to the smaller singlet-triplet energy gap(△E_(ST)),and remarkable photostability under green light exposure at 530nm(8.9 mW/cm^(2)).More importantly,TBBC was demonstrated effectiveness in selective staining and photodynamic killing of Escherichia coli(E.coli)in vitro probably due to its optimal molecular size compared with TBC and TBBC-C8.Therefore,TBBC will have great potential as a novel AIE photosensitizer to apply in the discrimination and selective sterilization between Gram-positive and Gram-negative bacteria.
基金supported by the project of the National Key Research and Development Program of China(No.2022YFA1207600)the National Natural Science Foundation of China(Nos.62005294,62375272)TIPC Director’s Fund.
文摘The complexity of cancer therapy has led to the emergence of combination therapy as a promising approach to enhance treatment efficacy and safety.The integration of glutathione(GSH)-activatable two-photon photodynamic therapy(TP-PDT)and chemodynamic therapy(CDT)offers the possibility to advance precision and efficacy in anti-cancer treatments.In this study,a GSH-activatable photosensitizer(PS),namely copper-elsinochrome(CuEC),is synthesized and utilized for combination second nearinfrared(NIR-II)TP-PDT/CDT.The Cu^(2+)acts as a“lock”,suppressing the fluorescence and^(1)O_(2)generation ability of EC in a normal physiological environment(“OFF”state).However,the overexpressed GSH in the tumor microenvironment acts as the“key”,resulting in the release of EC(“ON”state)and Cu^(+)(reduced by GSH).The released EC can be utilized for fluorescence imaging and TP-PDT under NIR-II(λ=1000 nm)two-photon excitation,while Cu+can generate highly toxic hydroxyl radicals(•OH)via Fenton-like reaction for CDT.Additionally,this process consumes GSH and diminishes the tumor’s antioxidant capacity,thereby augmenting the efficacy of combination therapy.The CuEC achieves significant tumor cell ablation in both 2D monolayer cells and 3D multicellular tumor spheres through the combination of NIR-II TP-PDT and CDT.
基金supported by the National Natural Science Foundation of China(No.82003372)the Medical and Health Technology Project of Zhejiang Province(No.2024KY984),China.
文摘Basal cell carcinoma(BCC)and cutaneous squamous cell carcinoma(cSCC),as certain forms of nonmelanoma skin cancer(NMSC)or keratinocyte carcinoma,are the most common forms of malignant neoplasms worldwide(Sharp et al.,2024).BCC and cSCC have been identified as two major components of NMSC,comprising one-third of all malignancies(Burton et al.,2016).Generally speaking,patients with NMSC tend to have relatively favorable survival outcomes,while different histopathological subtypes of NMSC exhibit distinct biological behaviors(Stătescu et al.,2023).
