An upconversion nanoparticle(NaErF_(4)∶Yb/Tm@NaLuF_(4)∶Yb@NaLuF_(4)∶Nd/Yb@NaLuF_(4),noted as UC)was designed,emitting strong red light by 808 nm laser.The mesoporous silica(mSiO_(2))shell co‑doped with chlorin e6(C...An upconversion nanoparticle(NaErF_(4)∶Yb/Tm@NaLuF_(4)∶Yb@NaLuF_(4)∶Nd/Yb@NaLuF_(4),noted as UC)was designed,emitting strong red light by 808 nm laser.The mesoporous silica(mSiO_(2))shell co‑doped with chlorin e6(Ce6)and triethoxy(1H,1H,2H,2H‑nonafluorohexyl)silane(TFS)was coated on the outer layer of UC,and then a layer of HKUST‑1 shell was coated.The obtained nanocomposite UC@Ce6/TFS@mSiO_(2)@HKUST‑1(noted as UCTSH)was used for the synergistic treatment of chemodynamic therapy(CDT)and photodynamic therapy(PDT).Interestingly,the nanostructures can specifically re lease Cu^(2+)in the acidic tumor microenvironment.Cu^(2+)reacts with excess hydrogen peroxide(H_(2)O_(2))in the tumor microenvironment to form cytotoxic hydroxyl radical.Secondly,Ce6,with the action of oxygen‑carrying TFS,selectively produces a large amount of singlet oxygen by 808 nm laser irradiation.UCTSH can enhance the anti‑tumor effects of PDT and CDT by increasing the production level of reactive oxygen species,without causing damage to normal cells.展开更多
Diatoms,as natural sources of porous silica,have important potential for biomedical applications.Biohybrid microrobots also show promise for targeted delivery;however,research on converting diatoms into biohybrid micr...Diatoms,as natural sources of porous silica,have important potential for biomedical applications.Biohybrid microrobots also show promise for targeted delivery;however,research on converting diatoms into biohybrid microrobots and exploiting their intrinsic properties for cancer treatment remains limited.In this study,Thalassiosira weissflogii was transformed into biohybrid microrobots(Mag-Diatoms)while retaining its natural chlorophyll,thereby enabling Mag-Diatom-mediated photodynamic therapy(PDT)without additional drug modification.In this system,Mag-Diatoms act ed as microrobots,and their intrinsic chlorophyll serve d as a photosensitizer,exhibiting excellent biological safety.The autonomous closed-loop motion of the Mag-Diatoms was achieved using an artificial intelligence algorithm,which enabled controlled navigation along a preset trajectory.Mag-Diatoms also exhibited the ability to traverse narrow slits and target cancer cells within a cellular environment.The PDT effect was validated in vitro using human malignant glioblastoma(GBM)cell lines and primary cells derived from patients.The results revealed that the cell viability was closely related to the Mag-Diatom concentration,laser intensity,and irradiation time.Under combined Mag-Diatoms and laser treatment,viability decreased to 19.5%in primary cells and 3.6%in cell line models.Moreover,in vivo experiments using a mouse glioma model revealed that Mag-Diatom-mediated PDT effectively suppressed GBM progression.These findings highlight the potential of diatom-derived biohybrid microrobots,leveraging their natural properties,as a novel material and solution for PDT-based GBM therapy.展开更多
Novel antibacterial strategies such as antibacterial photodynamic therapy(aPDT)and photothermal therapy(PTT)have gained significant attention,however,relying on a single-treatment approach still faces challenges of in...Novel antibacterial strategies such as antibacterial photodynamic therapy(aPDT)and photothermal therapy(PTT)have gained significant attention,however,relying on a single-treatment approach still faces challenges of insufficient therapeutic efficiency and the potential for drug resistance.In this study,a multimodal synergistic antibacterial nanoplatform by coupling a carbon monoxide(CO)donor(4-(3-hydroxy-4-oxo-4H-chromen-2-yl)benzoic acid(4-BA))with carbon dots(CDs)is developed,referred to as CDs-CO,which integrates multiple antibacterial modes of aPDT,PTT,and gas therapy.This nanoplatform is designed for highly efficient antibacterial action with a low risk of inducing drug resistance.CDs are engineered to possess tailored functions,including deep-red light-triggered heat and singlet oxygen(^(1)O_(2))production.After modification with 4-BA and exposure to 660 nm laser irradiation,CDs-CO exhibits favorable photothermal conversion efficiency(η=52.7%),robust ^(1)O_(2) generation,and ^(1)O_(2)-activated CO release.Antibacterial experiments demonstrated the excellent sterilization effects of CDs-CO against both Escherichia coli(E.coli)and Staphylococcus aureus(S.aureus),underscoring the enhanced antibacterial efficiency of this multimodal nanoplatform.This study offers a rational approach for designing multimodal synergistic antibacterial platforms,highlighting their potential for effectively treating bacterial infections.展开更多
Thermally activated delayed fluorescence(TADF) emitters show great potential in photodynamic therapy(PDT) and bioimaging,leveraging their structural adaptability,efficient reverse intersystem crossing(RISC),robust pho...Thermally activated delayed fluorescence(TADF) emitters show great potential in photodynamic therapy(PDT) and bioimaging,leveraging their structural adaptability,efficient reverse intersystem crossing(RISC),robust photosensitizing capability,and high photoluminescence quantum yields(PLQYs).Herein,we developed a new class of donor-acceptor-donor(D-A-D)-type TADF materials by connecting the highly twisted indolizine-benzophenone electron acceptors with a series of electron donors including phenoxazine,phenothiazine and 9,9-dimethyl-9,10-dihydroacridine.These materials exhibit enhanced TADF properties,aggregation-induced emission(AIE),alongside high reactive oxygen species(ROS) generation efficiency,effectively mitigating aggregation-caused quenching observed in traditional fluorophores.Among them,IDP-p-PXZ,incorporating the phenoxazine donor,stands out with the smallest singlet-triplet splitting energy(ΔE_(ST)) and the highest spin-orbit coupling matrix elements(SOCMEs).Upon encapsulation into 1,2-distearoyl-sn-glycero-3-phosphoethanolamine-N-[methoxy(polyethylene glycol)-2000](DSPE-PEG2000) nanoparticles(NPs),IDP-p-PXZ demonstrates extended delayed fluorescence lifetimes in air,an exceptionally fast intersystem crossing(ISC) rate constant(k_(ISC)) of 3.4×10^(7)s^(-1),and a radiative rate constant(k_(r)) of 5.05×10^(6)s^(-1).These NPs exhibit superior biocompatibility,efficient cellular internalization,and potent ROS production,enabling effective simultaneous PDT and confocal fluorescence imaging in HeLa cells.展开更多
Background:Photodynamic therapy(PDT)may eradicate residual malignant cells following sarcoma resection,through reactive oxygen species(ROS)mediated cytotoxicity,thus improve clinical outcomes.This study aims to assess...Background:Photodynamic therapy(PDT)may eradicate residual malignant cells following sarcoma resection,through reactive oxygen species(ROS)mediated cytotoxicity,thus improve clinical outcomes.This study aims to assess the efficacy of 5-aminolevulinic acid(5-ALA)as a photosensitizer in combination with red light(RL)for PDT of bone sarcoma cells in vitro.Methods:Three bone sarcoma cell lines underwent treatment with 5-ALA and RL or sham-RL(SL).5-ALA uptake was assessed using flow cytometry.Production of ROS was measured using CellROX Green staining and fluorescence microscopy.Cell viability was assessed using Cell Counting Kit-8 assays.Results:All cell lines showed significant 5-ALA uptake in comparison to the 0 mM control(p<0.05).Production of ROS was significantly increased in cells treated with 5-ALA and RL,compared to those treated with RL and no 5-ALA or SL(p<0.05).Viability was significantly reduced in cells treated with 5-ALA and RL,compared to SL(p<0.05).At 72 h post-treatment,cell viability ranged from 6%-12%in 0.5 mM 5-ALA and RL-treated cells vs.90%-137%in 0.5 mM 5-ALA and SL-treated cells.Conclusion:5-ALA-based PDT led to the desired increased production of ROS and reduction in cell viability in all cell lines.These preliminary in vitro results warrant further study with multicellular spheroid or animal models and suggest PDT has potential to be used as an adjuvant therapy to surgical resection in sarcoma management.展开更多
Objectives:Photodynamic therapy(PDT)is a minimally invasive method used in the treatment of various cancers and skin diseases,but it is not widely used in bone cancer,where the current therapy is often not effective a...Objectives:Photodynamic therapy(PDT)is a minimally invasive method used in the treatment of various cancers and skin diseases,but it is not widely used in bone cancer,where the current therapy is often not effective and accompanied by side effects.Alternative and more effective therapies like PDT are needed.In this in-vitro study,the effect of the photosensitizer(PS)chlorin e6(Ce6)on cancerous bone tumor cells using PDT was examined.Methods:A total of 27 tissue specimens from patients with primary bone cancers or bone metastases of different origins were genetically characterized and treated with PDT.Following a 24-h incubation,cell viability was determined,and the effect of PDT on cell migration was analyzed over 48 h.Results:We could demonstrate that the effect on proliferation of PDT in combination with the PS Ce6 was best in cells isolated from primary osteosarcoma and in bone metastases from mammary carcinomas.Besides proliferation,PDT was also effective in inhibiting the migration of these cells.A statistically significant correlation between the PDT effect and CD164 gene expression was detected,indicating that a high expression of this gene could result in a higher effectiveness of the photodynamic treatment.Conclusion:This study analyzes for the first time the effect of PDT in bone cancers and metastases and shows the potential of treating these cancer types with Ce6 PDT.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
Synergistic therapy using multiple modalities is a highly promising therapeutic strategy.Near-infrared-Ⅱ(NIR-Ⅱ)fluorescence imaging,with its deep penetration and high fidelity,has frequently been employed in the lit...Synergistic therapy using multiple modalities is a highly promising therapeutic strategy.Near-infrared-Ⅱ(NIR-Ⅱ)fluorescence imaging,with its deep penetration and high fidelity,has frequently been employed in the literature to guide and assist treatment.Herein,we report the development of a NIR-Ⅱfluorescence imaging guided multi-therapy platform PDI-DS NPs,which integrates a novel activatable phototheranostic agent PDI-DBU,a H_(2)S donor DPS and an amphiphilic polymer DSPE-m PEG2000.In order to maximize redshift of absorption and emission of PDI derivatives,we introduced an electron donating group DBU on PDI to obtain PDI-DBU.PDI-DBU exhibits a distinct absorption band at 700-900 nm and demonstrates excellent NIR-Ⅱfluorescence emission/imaging properties and good photothermal effects under 808 nm laser irradiation.More importantly,under 808 nm laser irradiation,PDI-DBU could be oxidized,and the photodynamic effect of the material could be subsequently activated under 530 nm laser irradiation,achieving the combination of photothermal and activatable photodynamic dual modality treatment.The H_(2)S donor DPS,when triggered by the abundant glutathione(GSH)within the tumor microenvironment(TME),is capable of generating H_(2)S.On one hand,H_(2)S can inhibit tumor growth by disrupting mitochondrial function,on the other hand,it can also repress the expression of heat shock protein 90(HSP90),thereby reversing tumor cell resistance mechanism against photothermal therapy.The utilization of PDI-DS NPs combined with DPS for efficient tumor ablation has been successfully demonstrated both in vitro and in vivo.This synergistic therapeutic platform thus offers a promising strategy in the field of NIR-Ⅱfluorescence imaging guided tumor therapy.展开更多
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
Two-dimensional(2D)metal-organic frameworks(MOFs)have emerged as promising photosensitizers in photodynamic therapy in recent years.In comparison to bulk MOFs,constructing 2D MOFs can increase the presence of active s...Two-dimensional(2D)metal-organic frameworks(MOFs)have emerged as promising photosensitizers in photodynamic therapy in recent years.In comparison to bulk MOFs,constructing 2D MOFs can increase the presence of active sites through increasing the surface area ratio.Herein,we report a simple solventmediated synthesis method for preparation of 2D porphyrin-based MOF(In-TCPP)nanosheets without the addition of any surfactants as an efficient photosensitizer for enhancing photodynamic antibacterial therapy.The accurate regulation of the morphology and size of 2D In-TCPP nanosheets can be achieved by varying the ratio of water to N,N-dimethylformamide solvent with the appropriate assistance of pyridine.The optimal synthesized 2D In-TCPP nanosheets exhibit a diameter of 70–120 nm and a thickness of 21.5–27.4 nm.Promisingly,2D In-TCPP nanosheets produce a higher amount of ^(1)O_(2) when exposed to660 nm laser compared to the In-TCPP bulk,indicating that the smaller nanosheets possess more active sites for reactive oxygen species generation and can greatly improve the antibacterial photodynamic therapeutic effect.Both the in vitro and in vivo results prove that the In-TCPP nanosheets can be used as a photosensitizer for efficient photodynamic antibacterial therapy to kill S.aureus and promote wound healing.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)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
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
The efficient and safe strategy is highly desirable for effective tumor treatment,yet the development is still unsatisfied.In this work,we develop a photo-accelerated nanoplatform for image-guided synergistic chemo-ph...The efficient and safe strategy is highly desirable for effective tumor treatment,yet the development is still unsatisfied.In this work,we develop a photo-accelerated nanoplatform for image-guided synergistic chemo-photodynamic therapy.We first synthesize an aggregation-induced emission luminogen(AIEgen)with outstanding type-Ⅰ and type-Ⅱ photodynamic therapy(PDT)properties.By integrating the high-performance AIEgen with a hypoxia-responsive prodrug and camouflaging with M1 macrophage membrane,a tumor-targeting theranostic agent is created.Upon light trigger,the type-Ⅱ PDT process depletes oxygen in the tumor microenvironment,exacerbating hypoxia and promoting prodrug activation.Meanwhile,the type-Ⅰ PDT mechanism,being less reliant on oxygen,ensures that the overall PDT efficacy remains largely unaffected.Consequently,this light-triggered synergistic PDT-chemotherapy system demonstrates enhanced therapeutic performance.In vivo fluorescence imaging precisely delineates tumor sites,guiding subsequent treatment.The photo-triggered prodrug activation and PDT significantly boost the therapeutic outcomes of the tumor.This approach presents a compelling solution for targeted and efficient tumor treatment.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
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)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
Porphyrin-based photodynamic therapy(PDT)has emerged as a promising approach in clinic.However,its therapeutic efficacy is remarkedly constrained due to the intrinsic hydrophobicity of porphyrins and their limited abs...Porphyrin-based photodynamic therapy(PDT)has emerged as a promising approach in clinic.However,its therapeutic efficacy is remarkedly constrained due to the intrinsic hydrophobicity of porphyrins and their limited absorption in the near-infrared(NIR)region.Inspired by the unique supramolecular structures and optical properties of pigment-binding proteins during photosynthesis,we herein developed a carbon dot derived from porphyrin and amino acid mixture(TPP-AA-CDs)for efficient PDT.Having precisely tuned the optical properties of TPP-AA-CDs in the range of visible to NIR region,such a pigment-binding protein-mimicking system leveraged the hydrophilic amino acid-hybrid framework as a light-harvesting scaffold to support the hydrophobic porphyrin centre.TPP-AA-CDs exhibited enhanced light-harvesting efficiency in the presence of amino and hydroxyl residues from amino acid side chains,which facilitate the incorporation of porphyrin within the framework.Among the variants,histidine-derived carbon dots(TPP-H-CDs)performed markedly improved PDT efficiency with high biocompatibility,leading to accelerated wound healing and boosted antitumor effects under NIR light irradiation.This light-harvesting pigment-binding protein-mimicking framework that scaffolded the porphyrin,offered a promising strategy for developing the next-generation of efficient NIR-absorbing materials with potential clinical translations.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
文摘An upconversion nanoparticle(NaErF_(4)∶Yb/Tm@NaLuF_(4)∶Yb@NaLuF_(4)∶Nd/Yb@NaLuF_(4),noted as UC)was designed,emitting strong red light by 808 nm laser.The mesoporous silica(mSiO_(2))shell co‑doped with chlorin e6(Ce6)and triethoxy(1H,1H,2H,2H‑nonafluorohexyl)silane(TFS)was coated on the outer layer of UC,and then a layer of HKUST‑1 shell was coated.The obtained nanocomposite UC@Ce6/TFS@mSiO_(2)@HKUST‑1(noted as UCTSH)was used for the synergistic treatment of chemodynamic therapy(CDT)and photodynamic therapy(PDT).Interestingly,the nanostructures can specifically re lease Cu^(2+)in the acidic tumor microenvironment.Cu^(2+)reacts with excess hydrogen peroxide(H_(2)O_(2))in the tumor microenvironment to form cytotoxic hydroxyl radical.Secondly,Ce6,with the action of oxygen‑carrying TFS,selectively produces a large amount of singlet oxygen by 808 nm laser irradiation.UCTSH can enhance the anti‑tumor effects of PDT and CDT by increasing the production level of reactive oxygen species,without causing damage to normal cells.
基金supported by the National Key R&D Program of China(No.2023YFB4705600)the National Natural Science Foundation of China(Nos.U23A20342,U20A20380,62273331,62127811,and 82373342)+4 种基金CAS Project for Young Scientists in Basic Research(No.YSBR-036)New Cornerstone Science Foundation through the XPLORER PRIZE,CAS/SAFEA International Partnership Program for Creative Research Teams,the Science and Technology Planning Project of Liaoning Province(No.2021JH1/10400049)Shengjing Hospital of China Medical University 345 Talent Project(No.1000801592)the Joint Project of Liaoning Province(No.2023JH2/101700202)“the Fundamental Research Funds for the Central Universities”,South-Central Minzu University(No.CZQ 25014).
文摘Diatoms,as natural sources of porous silica,have important potential for biomedical applications.Biohybrid microrobots also show promise for targeted delivery;however,research on converting diatoms into biohybrid microrobots and exploiting their intrinsic properties for cancer treatment remains limited.In this study,Thalassiosira weissflogii was transformed into biohybrid microrobots(Mag-Diatoms)while retaining its natural chlorophyll,thereby enabling Mag-Diatom-mediated photodynamic therapy(PDT)without additional drug modification.In this system,Mag-Diatoms act ed as microrobots,and their intrinsic chlorophyll serve d as a photosensitizer,exhibiting excellent biological safety.The autonomous closed-loop motion of the Mag-Diatoms was achieved using an artificial intelligence algorithm,which enabled controlled navigation along a preset trajectory.Mag-Diatoms also exhibited the ability to traverse narrow slits and target cancer cells within a cellular environment.The PDT effect was validated in vitro using human malignant glioblastoma(GBM)cell lines and primary cells derived from patients.The results revealed that the cell viability was closely related to the Mag-Diatom concentration,laser intensity,and irradiation time.Under combined Mag-Diatoms and laser treatment,viability decreased to 19.5%in primary cells and 3.6%in cell line models.Moreover,in vivo experiments using a mouse glioma model revealed that Mag-Diatom-mediated PDT effectively suppressed GBM progression.These findings highlight the potential of diatom-derived biohybrid microrobots,leveraging their natural properties,as a novel material and solution for PDT-based GBM therapy.
基金supported by the National Natural Science Foundation of China(No.52173126)China Postdoctoral Science Foundation(No.2024M751152).
文摘Novel antibacterial strategies such as antibacterial photodynamic therapy(aPDT)and photothermal therapy(PTT)have gained significant attention,however,relying on a single-treatment approach still faces challenges of insufficient therapeutic efficiency and the potential for drug resistance.In this study,a multimodal synergistic antibacterial nanoplatform by coupling a carbon monoxide(CO)donor(4-(3-hydroxy-4-oxo-4H-chromen-2-yl)benzoic acid(4-BA))with carbon dots(CDs)is developed,referred to as CDs-CO,which integrates multiple antibacterial modes of aPDT,PTT,and gas therapy.This nanoplatform is designed for highly efficient antibacterial action with a low risk of inducing drug resistance.CDs are engineered to possess tailored functions,including deep-red light-triggered heat and singlet oxygen(^(1)O_(2))production.After modification with 4-BA and exposure to 660 nm laser irradiation,CDs-CO exhibits favorable photothermal conversion efficiency(η=52.7%),robust ^(1)O_(2) generation,and ^(1)O_(2)-activated CO release.Antibacterial experiments demonstrated the excellent sterilization effects of CDs-CO against both Escherichia coli(E.coli)and Staphylococcus aureus(S.aureus),underscoring the enhanced antibacterial efficiency of this multimodal nanoplatform.This study offers a rational approach for designing multimodal synergistic antibacterial platforms,highlighting their potential for effectively treating bacterial infections.
基金supported by the National Natural Science Foundation of China (No.22405062)the Guangdong Basic and Applied Basic Research Foundation (No.2021A1515110869)+2 种基金the Shenzhen Science and Technology Program (No.ZDSYS20210623091813040)Innovation Program of Zhanjiang (No.2020LHJH005)Funds for Ph.D.researchers of Guangdong Medical University in 2025 (No.4SG25007G)。
文摘Thermally activated delayed fluorescence(TADF) emitters show great potential in photodynamic therapy(PDT) and bioimaging,leveraging their structural adaptability,efficient reverse intersystem crossing(RISC),robust photosensitizing capability,and high photoluminescence quantum yields(PLQYs).Herein,we developed a new class of donor-acceptor-donor(D-A-D)-type TADF materials by connecting the highly twisted indolizine-benzophenone electron acceptors with a series of electron donors including phenoxazine,phenothiazine and 9,9-dimethyl-9,10-dihydroacridine.These materials exhibit enhanced TADF properties,aggregation-induced emission(AIE),alongside high reactive oxygen species(ROS) generation efficiency,effectively mitigating aggregation-caused quenching observed in traditional fluorophores.Among them,IDP-p-PXZ,incorporating the phenoxazine donor,stands out with the smallest singlet-triplet splitting energy(ΔE_(ST)) and the highest spin-orbit coupling matrix elements(SOCMEs).Upon encapsulation into 1,2-distearoyl-sn-glycero-3-phosphoethanolamine-N-[methoxy(polyethylene glycol)-2000](DSPE-PEG2000) nanoparticles(NPs),IDP-p-PXZ demonstrates extended delayed fluorescence lifetimes in air,an exceptionally fast intersystem crossing(ISC) rate constant(k_(ISC)) of 3.4×10^(7)s^(-1),and a radiative rate constant(k_(r)) of 5.05×10^(6)s^(-1).These NPs exhibit superior biocompatibility,efficient cellular internalization,and potent ROS production,enabling effective simultaneous PDT and confocal fluorescence imaging in HeLa cells.
文摘Background:Photodynamic therapy(PDT)may eradicate residual malignant cells following sarcoma resection,through reactive oxygen species(ROS)mediated cytotoxicity,thus improve clinical outcomes.This study aims to assess the efficacy of 5-aminolevulinic acid(5-ALA)as a photosensitizer in combination with red light(RL)for PDT of bone sarcoma cells in vitro.Methods:Three bone sarcoma cell lines underwent treatment with 5-ALA and RL or sham-RL(SL).5-ALA uptake was assessed using flow cytometry.Production of ROS was measured using CellROX Green staining and fluorescence microscopy.Cell viability was assessed using Cell Counting Kit-8 assays.Results:All cell lines showed significant 5-ALA uptake in comparison to the 0 mM control(p<0.05).Production of ROS was significantly increased in cells treated with 5-ALA and RL,compared to those treated with RL and no 5-ALA or SL(p<0.05).Viability was significantly reduced in cells treated with 5-ALA and RL,compared to SL(p<0.05).At 72 h post-treatment,cell viability ranged from 6%-12%in 0.5 mM 5-ALA and RL-treated cells vs.90%-137%in 0.5 mM 5-ALA and SL-treated cells.Conclusion:5-ALA-based PDT led to the desired increased production of ROS and reduction in cell viability in all cell lines.These preliminary in vitro results warrant further study with multicellular spheroid or animal models and suggest PDT has potential to be used as an adjuvant therapy to surgical resection in sarcoma management.
文摘Objectives:Photodynamic therapy(PDT)is a minimally invasive method used in the treatment of various cancers and skin diseases,but it is not widely used in bone cancer,where the current therapy is often not effective and accompanied by side effects.Alternative and more effective therapies like PDT are needed.In this in-vitro study,the effect of the photosensitizer(PS)chlorin e6(Ce6)on cancerous bone tumor cells using PDT was examined.Methods:A total of 27 tissue specimens from patients with primary bone cancers or bone metastases of different origins were genetically characterized and treated with PDT.Following a 24-h incubation,cell viability was determined,and the effect of PDT on cell migration was analyzed over 48 h.Results:We could demonstrate that the effect on proliferation of PDT in combination with the PS Ce6 was best in cells isolated from primary osteosarcoma and in bone metastases from mammary carcinomas.Besides proliferation,PDT was also effective in inhibiting the migration of these cells.A statistically significant correlation between the PDT effect and CD164 gene expression was detected,indicating that a high expression of this gene could result in a higher effectiveness of the photodynamic treatment.Conclusion:This study analyzes for the first time the effect of PDT in bone cancers and metastases and shows the potential of treating these cancer types with Ce6 PDT.
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 National Natural Science Foundation of China(No.22274148)the Science and Technology Development Foundation of Jilin Province(Nos.20220204098YY,20230402045GH,20230402018GH,YDZJ202201ZYTS359,YDZJ202201ZYTS351,20240404070ZP,SKL202302030)the Jilin Province Development and Reform Commission’s Innovation Capacity Building Program(No.2023C041-8)。
文摘Synergistic therapy using multiple modalities is a highly promising therapeutic strategy.Near-infrared-Ⅱ(NIR-Ⅱ)fluorescence imaging,with its deep penetration and high fidelity,has frequently been employed in the literature to guide and assist treatment.Herein,we report the development of a NIR-Ⅱfluorescence imaging guided multi-therapy platform PDI-DS NPs,which integrates a novel activatable phototheranostic agent PDI-DBU,a H_(2)S donor DPS and an amphiphilic polymer DSPE-m PEG2000.In order to maximize redshift of absorption and emission of PDI derivatives,we introduced an electron donating group DBU on PDI to obtain PDI-DBU.PDI-DBU exhibits a distinct absorption band at 700-900 nm and demonstrates excellent NIR-Ⅱfluorescence emission/imaging properties and good photothermal effects under 808 nm laser irradiation.More importantly,under 808 nm laser irradiation,PDI-DBU could be oxidized,and the photodynamic effect of the material could be subsequently activated under 530 nm laser irradiation,achieving the combination of photothermal and activatable photodynamic dual modality treatment.The H_(2)S donor DPS,when triggered by the abundant glutathione(GSH)within the tumor microenvironment(TME),is capable of generating H_(2)S.On one hand,H_(2)S can inhibit tumor growth by disrupting mitochondrial function,on the other hand,it can also repress the expression of heat shock protein 90(HSP90),thereby reversing tumor cell resistance mechanism against photothermal therapy.The utilization of PDI-DS NPs combined with DPS for efficient tumor ablation has been successfully demonstrated both in vitro and in vivo.This synergistic therapeutic platform thus offers a promising strategy in the field of NIR-Ⅱfluorescence imaging guided tumor therapy.
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 National Natural Science Foundation of China(Nos.52102348,22171123,and 22271130)the Science and Technology Innovation Talent Program of University in Henan Province(No.23HASTIT016)+3 种基金the Natural Science Foundation of Henan Province(No.242300420199)International Science and Technology Cooperation Project of Henan Province of China(No.242102520016)the Key Scientific Research Projects of Universities in Henan Province(No.24A350006)the funding support from the National Natural Science Foundation of China-Excellent Young Scientists Fund(Hong Kong and Macao)(No.52122002)。
文摘Two-dimensional(2D)metal-organic frameworks(MOFs)have emerged as promising photosensitizers in photodynamic therapy in recent years.In comparison to bulk MOFs,constructing 2D MOFs can increase the presence of active sites through increasing the surface area ratio.Herein,we report a simple solventmediated synthesis method for preparation of 2D porphyrin-based MOF(In-TCPP)nanosheets without the addition of any surfactants as an efficient photosensitizer for enhancing photodynamic antibacterial therapy.The accurate regulation of the morphology and size of 2D In-TCPP nanosheets can be achieved by varying the ratio of water to N,N-dimethylformamide solvent with the appropriate assistance of pyridine.The optimal synthesized 2D In-TCPP nanosheets exhibit a diameter of 70–120 nm and a thickness of 21.5–27.4 nm.Promisingly,2D In-TCPP nanosheets produce a higher amount of ^(1)O_(2) when exposed to660 nm laser compared to the In-TCPP bulk,indicating that the smaller nanosheets possess more active sites for reactive oxygen species generation and can greatly improve the antibacterial photodynamic therapeutic effect.Both the in vitro and in vivo results prove that the In-TCPP nanosheets can be used as a photosensitizer for efficient photodynamic antibacterial therapy to kill S.aureus and promote wound healing.
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 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.
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the financial support from the National Natural Science Foundation of China(Nos.32471462,82172081)Natural Science Foundation of Shanxi Province of China(Nos.202203021211240,202203021211230)+2 种基金Shanxi Province Higher Education“Billion Project”Science and Technology Guidance Project(No.BYJL032)Research Project Supported by Shanxi Scholarship Council of China(No.2023–101)Shanxi Province Graduate Research Innovation Project(No.2024KY387)。
文摘The efficient and safe strategy is highly desirable for effective tumor treatment,yet the development is still unsatisfied.In this work,we develop a photo-accelerated nanoplatform for image-guided synergistic chemo-photodynamic therapy.We first synthesize an aggregation-induced emission luminogen(AIEgen)with outstanding type-Ⅰ and type-Ⅱ photodynamic therapy(PDT)properties.By integrating the high-performance AIEgen with a hypoxia-responsive prodrug and camouflaging with M1 macrophage membrane,a tumor-targeting theranostic agent is created.Upon light trigger,the type-Ⅱ PDT process depletes oxygen in the tumor microenvironment,exacerbating hypoxia and promoting prodrug activation.Meanwhile,the type-Ⅰ PDT mechanism,being less reliant on oxygen,ensures that the overall PDT efficacy remains largely unaffected.Consequently,this light-triggered synergistic PDT-chemotherapy system demonstrates enhanced therapeutic performance.In vivo fluorescence imaging precisely delineates tumor sites,guiding subsequent treatment.The photo-triggered prodrug activation and PDT significantly boost the therapeutic outcomes of the tumor.This approach presents a compelling solution for targeted and efficient tumor treatment.
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.
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(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 by the Key Research and Development Joint Fund of the Department of Science and Technology of Liaoning Province(No.2021JH2/1030005)the General Program of the Education Department of Liaoning Province(No.JYTMS20230101)。
文摘Porphyrin-based photodynamic therapy(PDT)has emerged as a promising approach in clinic.However,its therapeutic efficacy is remarkedly constrained due to the intrinsic hydrophobicity of porphyrins and their limited absorption in the near-infrared(NIR)region.Inspired by the unique supramolecular structures and optical properties of pigment-binding proteins during photosynthesis,we herein developed a carbon dot derived from porphyrin and amino acid mixture(TPP-AA-CDs)for efficient PDT.Having precisely tuned the optical properties of TPP-AA-CDs in the range of visible to NIR region,such a pigment-binding protein-mimicking system leveraged the hydrophilic amino acid-hybrid framework as a light-harvesting scaffold to support the hydrophobic porphyrin centre.TPP-AA-CDs exhibited enhanced light-harvesting efficiency in the presence of amino and hydroxyl residues from amino acid side chains,which facilitate the incorporation of porphyrin within the framework.Among the variants,histidine-derived carbon dots(TPP-H-CDs)performed markedly improved PDT efficiency with high biocompatibility,leading to accelerated wound healing and boosted antitumor effects under NIR light irradiation.This light-harvesting pigment-binding protein-mimicking framework that scaffolded the porphyrin,offered a promising strategy for developing the next-generation of efficient NIR-absorbing materials with potential clinical translations.
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.
