An “Eigenstate Adjustment Autonomy” Model, permeated by the Nanosystem’s Fermi Level Pinning along with its rigid Conduction Band Discontinuity, compatible with pertinent Experimental Measurements, is being employe...An “Eigenstate Adjustment Autonomy” Model, permeated by the Nanosystem’s Fermi Level Pinning along with its rigid Conduction Band Discontinuity, compatible with pertinent Experimental Measurements, is being employed for studying how the Functional Eigenstate of the Two-Dimensional Electron Gas (2DEG) dwelling within the Quantum Well of a typical Semiconductor Nanoheterointerface evolves versus (cryptographically) selectable consecutive Cumulative Photon Dose values. Thus, it is ultimately discussed that the experimentally observed (after a Critical Cumulative Photon Dose) Phenomenon of 2DEG Negative Differential Mobility allows for the Nanosystem to exhibit an Effective Qubit Specific Functionality potentially conducive to (Telecommunication) Quantum Information Registering.展开更多
Charge transfer cocrystals,as a promising class of optoelectronic materials,have attracted significant attention due to their strong intermolecular interactions and efficient electronic coupling between donor and acce...Charge transfer cocrystals,as a promising class of optoelectronic materials,have attracted significant attention due to their strong intermolecular interactions and efficient electronic coupling between donor and acceptor molecules.However,a comprehensive understanding of their electronic structure and charge transfer dynamics remains crucial for optimizing their functional properties.In this study,the highly symmetrical polycyclic aromatic hydrocarbon coronene(COR)is selected as the electron donor,the 1,2,4,5-tetracyanobenzene(TCNB),known for its strong electron-accepting capability,is chosen as the electron acceptor.Using the microspacing in-air sublimation method,a highly oriented COR-TCNB organic charge-transfer cocrystal is successfully fabricated.Theoretical calculations,consistent with the experimental spectroscopic analysis,illuminate the electronic structure and charge transfer characteristics of the COR-TCNB cocrystal,and reveal charge redistribution and electron delocalization.The time-resolved fluorescence spectroscopy and transient transmission based on the femtosecond pump-probe method reveal the ultrafast photodynamics and charge transfer exciton formation.The present results exhibited the strong interaction of charge transfer and the existence of charge transfer excitons.This study provides new insights into structure-property relationships in charge transfer cocrystals,offering valuable guidelines for designing functional optoelectronic materials.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
With increasing drug resistance,Candida infections have posed serious threats to public health.Photodynamic therapy harnesses light to destroy pathomycete,providing a smart strategy for combating of Candida infections...With increasing drug resistance,Candida infections have posed serious threats to public health.Photodynamic therapy harnesses light to destroy pathomycete,providing a smart strategy for combating of Candida infections.However,due to lack of organelle targeting ability and bad extracellular polymeric substances penetrability,current photosensitizers(PSs)are far from desirable to clean biofilms and fight against drug resistance.Herein,a mitochondrion targeting aggregationinduced emission PS,LIQ-TPA-TZ,was developed for the efficient photodynamic treatment of oral Candida infection.LIQ-TPA-TZ has good singlet oxygen and hydroxyl radical generation ability,which can efficiently kill the Candida guilliermondii(C.guilliermondii)and eradicate the biofilm.It not only causes mitochondrial damage by disruption of mitochondrial respiratory chain and oxidative stress-related gene but also inhibits fungal adhesion and filamentous growth to prevent Candida colonization,mycelia growth and biofilm formation,which is favorable for eliminating the potential drug resistance.In the mouse oropharyngeal Candida biofilm infection model,LIQ-TPA-TZ significantly eliminates infection,alleviates inflammation,and accelerates mucosal defect healing.This study provides a favorable strategy for confronting drug resistance,which may be a potential Candidate for the treatment of Candida infection.展开更多
Metal complexes hold significant promise in tumor diagnosis and treatment.However,their potential applications in photodynamic therapy(PDT)are hindered by issues such as poor photostability,low yield of reactive oxyge...Metal complexes hold significant promise in tumor diagnosis and treatment.However,their potential applications in photodynamic therapy(PDT)are hindered by issues such as poor photostability,low yield of reactive oxygen species(ROS),and aggregation-induced ROS quenching.To address these challenges,we present a molecular self-assembly strategy utilizing aggregation-induced emission(AIE)conjugates for metal complexes.As a proof of concept,we synthesized a mitochondrial-targeting cyclometalated Ir(Ⅲ)photosensitizer Ir-TPE.This approach significantly enhances the photodynamic effect while mitigating the dark toxicity associated with AIE groups.Ir-TPE readily self-assembles into nanoaggregates in aqueous solution,leading to a significant production of ROS upon light irradiation.Photoirradiated Ir-TPE triggers multiple modes of death by excessively accumulating ROS in the mitochondria,resulting in mitochondrial DNA damage.This damage can lead to ferroptosis and autophagy,two forms of cell death that are highly cytotoxic to cancer cells.The aggregation-enhanced photodynamic effect of Ir-TPE significantly enhances the production of ROS,leading to a more pronounced cytotoxic effect.In vitro and in vivo experiments demonstrate this aggregation-enhanced PDT approach achieves effective in situ tumor eradication.This study not only addresses the limitations of metal complexes in terms of low ROS production due to aggregation but also highlights the potential of this strategy for enhancing ROS production in 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
The clinical application of tumor vaccines is hindered by challenges such as timeconsuming and costly production processes.In this context,in situ cancer vaccines represent a promising strategy by leveraging endogenou...The clinical application of tumor vaccines is hindered by challenges such as timeconsuming and costly production processes.In this context,in situ cancer vaccines represent a promising strategy by leveraging endogenous tumor antigens to elicit robust antitumor T cell responses.Herein,a photoactivatable tumor-targeting in situ nanovaccine,Lipo-D8-6,was constructed using cRGD-functionalized liposomes that co-encapsulated the photosensitizer chlorin e6 and a cleavable immunoadjuvant conjugate D8,allowing light-triggered synchronous activation of three therapeutic modules.Upon near-infrared light irradiation,Lipo-D8-6 generates reactive oxygen species that exert direct cytotoxicity on tumor cells and induce immunogenic cell death,while concurrently cleaving the responsive linker within D8 to achieve the controlled release of R848.In vivo biodistribution analysis confirmed the superior intratumoral accumulation of Lipo-D8-6,facilitating precise treatment.In a large-volume tumor model,the nanovaccine exhibited pronounced antitumor efficacy,accompanied by enhanced tumor infiltration of CD8t T cells.Overall,this work provides a simplified and effective approach for developing in situ nanovaccines that enable synergistic photodynamic immunotherapy with precise spatiotemporal control over immune activation.展开更多
Various chemical irrigants and drugs have been employed for intra-canal disinfection in root canal therapy(RCT).However,due to the complexity of root canal anatomy,many drugs still exhibit poor penetrability and antib...Various chemical irrigants and drugs have been employed for intra-canal disinfection in root canal therapy(RCT).However,due to the complexity of root canal anatomy,many drugs still exhibit poor penetrability and antibiotic resistance,leading to suboptimal treatment outcomes.Thus,it is challenging to remove the organic biofilms from root canals.In recent years,light-responsive therapy,with deeper tissue penetration than traditional treatments,has emerged as an effective RCT modality.Herein,this review summarizes the recent development of light-responsive nanomaterials for biofilm removal in RCT.The light-responsive nanomaterials and the corresponding therapeutic methods in RCT,including photodynamic therapy(PDT),photothermal therapy(PTT),and laser-activated therapy,are highlighted.Finally,the challenges that light-responsive nanomaterials and treatment modalities will encounter to conquer the biofilm in future RCT are discussed.This review is believed to significantly accelerate the future development of light-responsive nanomaterials for RCT from bench to bedside.展开更多
Rational design of multifunctional nanoplatforms capable of combining therapeutic effects with real-time monitoring of drug distribution and tumor status is emerging as a promising approach in cancer nanomedicine.Here...Rational design of multifunctional nanoplatforms capable of combining therapeutic effects with real-time monitoring of drug distribution and tumor status is emerging as a promising approach in cancer nanomedicine.Here,we introduce pyropheophorbide a-bisaminoquinoline conjugate lipid nanoparticles(PPBC LNPs)as a bimodal system for image-guided phototherapy in bladder cancer treatment.PPBC LNPs not only demonstrate both powerful photodynamic and photothermal effects upon light activation,but also exhibit potent autophagy blockage,effectively inducing bladder cancer cell death.Furthermore,PPBC LNPs possess remarkable photoacoustic(PA)and fluorescence(FL)imaging capabilities,enabling imaging with high-resolution,deep tissue penetration and high sensitivity for tracking drug biodistribution and phototherapy efficacy.Specifically,PA imaging confirms the efficient accumulation of PPBC LNPs within tumor and predicts therapeutic outcomes of photodynamic therapy,while FL imaging confirms their prolonged retention at the tumor site for up to 6 days.PPBC LNPs significantly suppress bladder tumor growth,with several tumors completely ablated following just two doses of the nanoparticles and laser treatment.Additionally,PPBC LNPs were formulated with lipid-based excipients and assembled using microfluidic technology to enhance biocompatibility,stability,and scalability,showing potential for clinical translation.This versatile nanoparticle represents a promising candidate for further development in bladder cancer therapy.展开更多
Intracellular bacteria(ICB),cloaked by the protective barriers of host cells,pose a formidable challenge to selective and efficient eradication.The employment of activatable photosensitizers based antibacterial photod...Intracellular bacteria(ICB),cloaked by the protective barriers of host cells,pose a formidable challenge to selective and efficient eradication.The employment of activatable photosensitizers based antibacterial photodynamic therapy(a PDT)holds significant potential for selective imaging and photo-inactivation of ICB while minimizing side effects on normal cells.Drawing inspiration from the elevated hypochlorous acid(HClO)levels in ICB infected phagocytes,herein we firstly designed and synthesized a series of HCl Oresponsive dinuclear Ru(Ⅱ)complexes(Ru1-Ru3)to achieve such a goal.Initially,the luminescence,^(1)O_(2)generation and a PDT activity of these Ru(Ⅱ)complexes were suppressed due to the quenching effect of the azo group,but were recovered after reaction with HCl O in solutions or within ICB infected phagocytes.The detailed results revealed that Ru1 and Ru3 could not only selectively visualize ICB,but also demonstrated remarkable a PDT activity against ICB,surpassing vancomycin both in vitro and in vivo.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
Near-infrared(NIR)theranostics have received considerable attention because of their advantages in precise diagnostic imaging and efficient simultaneous treatment and have achieved tremendous advancements in the last ...Near-infrared(NIR)theranostics have received considerable attention because of their advantages in precise diagnostic imaging and efficient simultaneous treatment and have achieved tremendous advancements in the last few years.However,their progress is severely restricted by the rarity of efficient second NIR(NIR-Ⅱ)responsive phototheranostic materials,especially in the NIR-Ⅱb region.Moreover,these materials often embarrass the quenching puzzle in the aggregative state,thus greatly reducing their theranostic performance.To overcome this limitation,we developed anti-quenching donor-acceptor-donor(D-AD)-conjugated oligomers with NIR-Ⅱb emission for high-performance NIR-Ⅱangiography and phototheranostics.Through multi-acceptor engineering,a series of multi-acceptor conjugated oligomer SU-n(n=1,2,and 5)with tunable acceptor ratios were synthesized,and their efficiency in anti-quenching NIR-Ⅱemission was demonstrated.When prepared into water-dispersed nanoparticles(NPs),SU-5 NPs exhibit bright NIR-Ⅱemission and dual phototherapy for photothermal therapy and photodynamic therapy simultaneously upon 808 nm light excitation.With these benefits,high-resolution whole-body and local angiography in vivo of SU-5 NPs were successfully realized in the NIR-Ⅱb window.Moreover,in vivo,theranostics experiments demonstrated the efficiency of SU-5 NPs in NIR-Ⅱimaging-guided complete tumor photoablation without any relapses with high biosafety.This work explores a practical multi-acceptor engineering strategy for developing anti-quenching theranostic materials,providing an efficient theranostic agent for efficient NIR-Ⅱb bioimaging and phototheranostics.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
Carbon dots(CDs)are an emerging class of zero-dimensional carbon nano optical materials that are as promising candidates for various applications.Through the exploration of scientific researchers,the optical band gap ...Carbon dots(CDs)are an emerging class of zero-dimensional carbon nano optical materials that are as promising candidates for various applications.Through the exploration of scientific researchers,the optical band gap of CDs has been continuously regulated and red-shifted from the initial blue-violet light to longer wavelengths.In recent years,CDs with near-infrared(NIR)absorption/emission have been gradually reported.Because NIR light has deeper penetration and lower scattering and is invisible to the human eye,it has great application prospects in the fields of biological imaging and treatment,information encryption,optical communications,etc.Although there are a few reviews on deep red to NIR CDs,they only focus on the single biomedical direction.There is still a lack of comprehensive reviews focusing on NIR(≥700 nm)absorption and luminescent CDs and their multifunctional applications.Based on our research group’s findings on NIR CDs,this review summarizes recent advancements in their preparation strategies and applications,points out the current shortcomings and challenges,and anticipates future development trajectories.展开更多
Photodynamic therapy(PDT)has been established as one of the most promising novel cancer therapies with fewer side-effects and enhanced efficacy compared to the currently available conventional treatments.However,its a...Photodynamic therapy(PDT)has been established as one of the most promising novel cancer therapies with fewer side-effects and enhanced efficacy compared to the currently available conventional treatments.However,its application has been hindered by the limitations that photosensitizers(PS)have.The combination of PS with metallic nanoparticles like platinum nanoparticles(PtNPs),can help to overcome these intrinsic drawbacks.In this work,the combination of PtNPs and the natural photosensitizer riboflavin(RF)is proposed.PtNPs are synthesized using RF(Pt@RF)as reducing and stabilizing agent in a one-step method,obtaining nanoparticles with mesoporous structure for UV triggered PDT.In view of possible future UV irradiation treatments,the degradation products of RF,ribitol(RB)and lumichrome(LC),this last being a photosensitizing byproduct,are also employed for the synthesis of porous PtNPs,obtaining Pt@LC and Pt@RB.When administered in vitro to lung cancer cells,all the samples elicit a strong decrease of cell viability and a decrease of intracellular ATP levels.The antitumoral effect of both Pt@RF and Pt@LC is triggered by UV-A irradiation.This antitumoral activity is caused by the induction of oxidative stress,shown in our study by the decrease in intracellular glutathione and increased expression of antioxidant enzymes.展开更多
Integrating photodynamic therapy(PDT)with immunosuppression reversal represents a promising synergistic approach to boost cancer immunotherapy.However,the complicated components and cumbersome preparation procedures o...Integrating photodynamic therapy(PDT)with immunosuppression reversal represents a promising synergistic approach to boost cancer immunotherapy.However,the complicated components and cumbersome preparation procedures of the currently developed nano drug delivery systems heavily hinder their further clinical translation.Herein,a reactive oxygen species(ROS)/photo dual-responsive amphipathic prodrug(denoted as PPTN)was designed and synthesized by linking NLG919,an indoleamine-2,3-dioxygenase(IDO)inhibitor,with the photosensitizer protoporphyrin IX(PpIX)by a thioketal moiety,and further modifying with mPEG2k.PPTN could self-assemble into nanoscale unimolecular micelles in aqueous solution without additional excipients,increasing tumor accumulation while effectively addressing the pronounced hydrophobicity challenge of PpIX.Upon light exposure,PPTN generated ROS,not only directly damaging cancer cells,but also trigger the breakage of thioketal bond to accelerate simultaneous release of NLG919.Therefore,PPTN potentially act as a promising ROS/photo dual-responsive carrier-free prodrug delivery system for controllable drug release and specific tumor therapy.Moreover,PPTN induced simultaneous PDT-triggered immunogenic cell death(ICD)effect and specific IDO blockade to boost immune response,exhibiting potent suppression efficacy against primary and distant tumors.Overall,with the superiorities of easily controllable preparation procedures,synchronous drug delivery and ROS/photo dual-responsiveness,such a prodrug unimolecular micelle may represent a promising nanoplatform for photoactivated-immunotherapy.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
文摘An “Eigenstate Adjustment Autonomy” Model, permeated by the Nanosystem’s Fermi Level Pinning along with its rigid Conduction Band Discontinuity, compatible with pertinent Experimental Measurements, is being employed for studying how the Functional Eigenstate of the Two-Dimensional Electron Gas (2DEG) dwelling within the Quantum Well of a typical Semiconductor Nanoheterointerface evolves versus (cryptographically) selectable consecutive Cumulative Photon Dose values. Thus, it is ultimately discussed that the experimentally observed (after a Critical Cumulative Photon Dose) Phenomenon of 2DEG Negative Differential Mobility allows for the Nanosystem to exhibit an Effective Qubit Specific Functionality potentially conducive to (Telecommunication) Quantum Information Registering.
基金the National Natural Science Foundation of China(No.51875006).
文摘Charge transfer cocrystals,as a promising class of optoelectronic materials,have attracted significant attention due to their strong intermolecular interactions and efficient electronic coupling between donor and acceptor molecules.However,a comprehensive understanding of their electronic structure and charge transfer dynamics remains crucial for optimizing their functional properties.In this study,the highly symmetrical polycyclic aromatic hydrocarbon coronene(COR)is selected as the electron donor,the 1,2,4,5-tetracyanobenzene(TCNB),known for its strong electron-accepting capability,is chosen as the electron acceptor.Using the microspacing in-air sublimation method,a highly oriented COR-TCNB organic charge-transfer cocrystal is successfully fabricated.Theoretical calculations,consistent with the experimental spectroscopic analysis,illuminate the electronic structure and charge transfer characteristics of the COR-TCNB cocrystal,and reveal charge redistribution and electron delocalization.The time-resolved fluorescence spectroscopy and transient transmission based on the femtosecond pump-probe method reveal the ultrafast photodynamics and charge transfer exciton formation.The present results exhibited the strong interaction of charge transfer and the existence of charge transfer excitons.This study provides new insights into structure-property relationships in charge transfer cocrystals,offering valuable guidelines for designing functional optoelectronic materials.
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.
基金supported by the National Natural Science Foundation of China(22177094)the Fundamental Research Funds for the Central Universities(YJ202419).
文摘With increasing drug resistance,Candida infections have posed serious threats to public health.Photodynamic therapy harnesses light to destroy pathomycete,providing a smart strategy for combating of Candida infections.However,due to lack of organelle targeting ability and bad extracellular polymeric substances penetrability,current photosensitizers(PSs)are far from desirable to clean biofilms and fight against drug resistance.Herein,a mitochondrion targeting aggregationinduced emission PS,LIQ-TPA-TZ,was developed for the efficient photodynamic treatment of oral Candida infection.LIQ-TPA-TZ has good singlet oxygen and hydroxyl radical generation ability,which can efficiently kill the Candida guilliermondii(C.guilliermondii)and eradicate the biofilm.It not only causes mitochondrial damage by disruption of mitochondrial respiratory chain and oxidative stress-related gene but also inhibits fungal adhesion and filamentous growth to prevent Candida colonization,mycelia growth and biofilm formation,which is favorable for eliminating the potential drug resistance.In the mouse oropharyngeal Candida biofilm infection model,LIQ-TPA-TZ significantly eliminates infection,alleviates inflammation,and accelerates mucosal defect healing.This study provides a favorable strategy for confronting drug resistance,which may be a potential Candidate for the treatment of Candida infection.
基金support from the National Natural Science Foundation of China(Nos.22277056,21977052)the Distinguished Young Scholars of Jiangsu Province(No.BK20230006)+2 种基金the Natural Science Foundation of Jiangsu Province(Nos.BK20230977,BK20231090)the Natural Science Foundation of the Higher Education Institutions of Jiangsu Province(No.23KJB150020)the Jiangsu Excellent Postdoctoral Program(No.2022ZB758)。
文摘Metal complexes hold significant promise in tumor diagnosis and treatment.However,their potential applications in photodynamic therapy(PDT)are hindered by issues such as poor photostability,low yield of reactive oxygen species(ROS),and aggregation-induced ROS quenching.To address these challenges,we present a molecular self-assembly strategy utilizing aggregation-induced emission(AIE)conjugates for metal complexes.As a proof of concept,we synthesized a mitochondrial-targeting cyclometalated Ir(Ⅲ)photosensitizer Ir-TPE.This approach significantly enhances the photodynamic effect while mitigating the dark toxicity associated with AIE groups.Ir-TPE readily self-assembles into nanoaggregates in aqueous solution,leading to a significant production of ROS upon light irradiation.Photoirradiated Ir-TPE triggers multiple modes of death by excessively accumulating ROS in the mitochondria,resulting in mitochondrial DNA damage.This damage can lead to ferroptosis and autophagy,two forms of cell death that are highly cytotoxic to cancer cells.The aggregation-enhanced photodynamic effect of Ir-TPE significantly enhances the production of ROS,leading to a more pronounced cytotoxic effect.In vitro and in vivo experiments demonstrate this aggregation-enhanced PDT approach achieves effective in situ tumor eradication.This study not only addresses the limitations of metal complexes in terms of low ROS production due to aggregation but also highlights the potential of this strategy for enhancing ROS production in 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 National Natural Science Foundation of China(22090011)Liaoning Binhai Laboratory(LBLB-2023-03)Fundamental Research Funds for the Central Universities(DUT22LAB608).
文摘The clinical application of tumor vaccines is hindered by challenges such as timeconsuming and costly production processes.In this context,in situ cancer vaccines represent a promising strategy by leveraging endogenous tumor antigens to elicit robust antitumor T cell responses.Herein,a photoactivatable tumor-targeting in situ nanovaccine,Lipo-D8-6,was constructed using cRGD-functionalized liposomes that co-encapsulated the photosensitizer chlorin e6 and a cleavable immunoadjuvant conjugate D8,allowing light-triggered synchronous activation of three therapeutic modules.Upon near-infrared light irradiation,Lipo-D8-6 generates reactive oxygen species that exert direct cytotoxicity on tumor cells and induce immunogenic cell death,while concurrently cleaving the responsive linker within D8 to achieve the controlled release of R848.In vivo biodistribution analysis confirmed the superior intratumoral accumulation of Lipo-D8-6,facilitating precise treatment.In a large-volume tumor model,the nanovaccine exhibited pronounced antitumor efficacy,accompanied by enhanced tumor infiltration of CD8t T cells.Overall,this work provides a simplified and effective approach for developing in situ nanovaccines that enable synergistic photodynamic immunotherapy with precise spatiotemporal control over immune activation.
基金supported by the Natural Science Foundation of Jiangsu Province(No.BK20200092)。
文摘Various chemical irrigants and drugs have been employed for intra-canal disinfection in root canal therapy(RCT).However,due to the complexity of root canal anatomy,many drugs still exhibit poor penetrability and antibiotic resistance,leading to suboptimal treatment outcomes.Thus,it is challenging to remove the organic biofilms from root canals.In recent years,light-responsive therapy,with deeper tissue penetration than traditional treatments,has emerged as an effective RCT modality.Herein,this review summarizes the recent development of light-responsive nanomaterials for biofilm removal in RCT.The light-responsive nanomaterials and the corresponding therapeutic methods in RCT,including photodynamic therapy(PDT),photothermal therapy(PTT),and laser-activated therapy,are highlighted.Finally,the challenges that light-responsive nanomaterials and treatment modalities will encounter to conquer the biofilm in future RCT are discussed.This review is believed to significantly accelerate the future development of light-responsive nanomaterials for RCT from bench to bedside.
文摘Rational design of multifunctional nanoplatforms capable of combining therapeutic effects with real-time monitoring of drug distribution and tumor status is emerging as a promising approach in cancer nanomedicine.Here,we introduce pyropheophorbide a-bisaminoquinoline conjugate lipid nanoparticles(PPBC LNPs)as a bimodal system for image-guided phototherapy in bladder cancer treatment.PPBC LNPs not only demonstrate both powerful photodynamic and photothermal effects upon light activation,but also exhibit potent autophagy blockage,effectively inducing bladder cancer cell death.Furthermore,PPBC LNPs possess remarkable photoacoustic(PA)and fluorescence(FL)imaging capabilities,enabling imaging with high-resolution,deep tissue penetration and high sensitivity for tracking drug biodistribution and phototherapy efficacy.Specifically,PA imaging confirms the efficient accumulation of PPBC LNPs within tumor and predicts therapeutic outcomes of photodynamic therapy,while FL imaging confirms their prolonged retention at the tumor site for up to 6 days.PPBC LNPs significantly suppress bladder tumor growth,with several tumors completely ablated following just two doses of the nanoparticles and laser treatment.Additionally,PPBC LNPs were formulated with lipid-based excipients and assembled using microfluidic technology to enhance biocompatibility,stability,and scalability,showing potential for clinical translation.This versatile nanoparticle represents a promising candidate for further development in bladder cancer therapy.
基金supported by National Natural Science Foundation of China(No.22371289)。
文摘Intracellular bacteria(ICB),cloaked by the protective barriers of host cells,pose a formidable challenge to selective and efficient eradication.The employment of activatable photosensitizers based antibacterial photodynamic therapy(a PDT)holds significant potential for selective imaging and photo-inactivation of ICB while minimizing side effects on normal cells.Drawing inspiration from the elevated hypochlorous acid(HClO)levels in ICB infected phagocytes,herein we firstly designed and synthesized a series of HCl Oresponsive dinuclear Ru(Ⅱ)complexes(Ru1-Ru3)to achieve such a goal.Initially,the luminescence,^(1)O_(2)generation and a PDT activity of these Ru(Ⅱ)complexes were suppressed due to the quenching effect of the azo group,but were recovered after reaction with HCl O in solutions or within ICB infected phagocytes.The detailed results revealed that Ru1 and Ru3 could not only selectively visualize ICB,but also demonstrated remarkable a PDT activity against ICB,surpassing vancomycin both in vitro and in vivo.
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 National Natural Science Foundation of China(Nos.52173135,22207024)the Natural Science Foundation of Jiangsu Province(No.BK20231523)+5 种基金Jiangsu Specially Appointed Professorship,Leading Talents of Innovation and Entrepreneurship of Gusu(No.ZXL2022496)the Suzhou Science and Technology Program(No.SKY2022039)funded by the China Postdoctoral Science Foundation(Nos.2022M712305,2023M742536)the Jiangsu Funding Program for Excellent Postdoctoral Talent(No.2023ZB011)the project funded by the Priority Academic Program Development(PAPD)of Jiangsu Higher Education InstitutionsSuzhou International Joint Laboratory for Diagnosis and Treatment of Brain Diseases。
文摘Near-infrared(NIR)theranostics have received considerable attention because of their advantages in precise diagnostic imaging and efficient simultaneous treatment and have achieved tremendous advancements in the last few years.However,their progress is severely restricted by the rarity of efficient second NIR(NIR-Ⅱ)responsive phototheranostic materials,especially in the NIR-Ⅱb region.Moreover,these materials often embarrass the quenching puzzle in the aggregative state,thus greatly reducing their theranostic performance.To overcome this limitation,we developed anti-quenching donor-acceptor-donor(D-AD)-conjugated oligomers with NIR-Ⅱb emission for high-performance NIR-Ⅱangiography and phototheranostics.Through multi-acceptor engineering,a series of multi-acceptor conjugated oligomer SU-n(n=1,2,and 5)with tunable acceptor ratios were synthesized,and their efficiency in anti-quenching NIR-Ⅱemission was demonstrated.When prepared into water-dispersed nanoparticles(NPs),SU-5 NPs exhibit bright NIR-Ⅱemission and dual phototherapy for photothermal therapy and photodynamic therapy simultaneously upon 808 nm light excitation.With these benefits,high-resolution whole-body and local angiography in vivo of SU-5 NPs were successfully realized in the NIR-Ⅱb window.Moreover,in vivo,theranostics experiments demonstrated the efficiency of SU-5 NPs in NIR-Ⅱimaging-guided complete tumor photoablation without any relapses with high biosafety.This work explores a practical multi-acceptor engineering strategy for developing anti-quenching theranostic materials,providing an efficient theranostic agent for efficient NIR-Ⅱb bioimaging and phototheranostics.
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 Science and Technology Development Fund of Macao SAR(Nos.0139/2022/A3,0007/2021/AKP,006/2022/ALC).
文摘Carbon dots(CDs)are an emerging class of zero-dimensional carbon nano optical materials that are as promising candidates for various applications.Through the exploration of scientific researchers,the optical band gap of CDs has been continuously regulated and red-shifted from the initial blue-violet light to longer wavelengths.In recent years,CDs with near-infrared(NIR)absorption/emission have been gradually reported.Because NIR light has deeper penetration and lower scattering and is invisible to the human eye,it has great application prospects in the fields of biological imaging and treatment,information encryption,optical communications,etc.Although there are a few reviews on deep red to NIR CDs,they only focus on the single biomedical direction.There is still a lack of comprehensive reviews focusing on NIR(≥700 nm)absorption and luminescent CDs and their multifunctional applications.Based on our research group’s findings on NIR CDs,this review summarizes recent advancements in their preparation strategies and applications,points out the current shortcomings and challenges,and anticipates future development trajectories.
基金funded by the Horizon Europe Project"PERSEUS"(No.101099423)financed by the Ministry of Universities under application 33.50.460A.752by the European Union NextGenerationEU/PRTR through a contract Margarita Salas from Universidade de Vigo.
文摘Photodynamic therapy(PDT)has been established as one of the most promising novel cancer therapies with fewer side-effects and enhanced efficacy compared to the currently available conventional treatments.However,its application has been hindered by the limitations that photosensitizers(PS)have.The combination of PS with metallic nanoparticles like platinum nanoparticles(PtNPs),can help to overcome these intrinsic drawbacks.In this work,the combination of PtNPs and the natural photosensitizer riboflavin(RF)is proposed.PtNPs are synthesized using RF(Pt@RF)as reducing and stabilizing agent in a one-step method,obtaining nanoparticles with mesoporous structure for UV triggered PDT.In view of possible future UV irradiation treatments,the degradation products of RF,ribitol(RB)and lumichrome(LC),this last being a photosensitizing byproduct,are also employed for the synthesis of porous PtNPs,obtaining Pt@LC and Pt@RB.When administered in vitro to lung cancer cells,all the samples elicit a strong decrease of cell viability and a decrease of intracellular ATP levels.The antitumoral effect of both Pt@RF and Pt@LC is triggered by UV-A irradiation.This antitumoral activity is caused by the induction of oxidative stress,shown in our study by the decrease in intracellular glutathione and increased expression of antioxidant enzymes.
基金supported by the National Natural Science Foundation of China(82373811,82574333,82504683)Natural Science Foundation of Guangdong Province(2024A1515012132).
文摘Integrating photodynamic therapy(PDT)with immunosuppression reversal represents a promising synergistic approach to boost cancer immunotherapy.However,the complicated components and cumbersome preparation procedures of the currently developed nano drug delivery systems heavily hinder their further clinical translation.Herein,a reactive oxygen species(ROS)/photo dual-responsive amphipathic prodrug(denoted as PPTN)was designed and synthesized by linking NLG919,an indoleamine-2,3-dioxygenase(IDO)inhibitor,with the photosensitizer protoporphyrin IX(PpIX)by a thioketal moiety,and further modifying with mPEG2k.PPTN could self-assemble into nanoscale unimolecular micelles in aqueous solution without additional excipients,increasing tumor accumulation while effectively addressing the pronounced hydrophobicity challenge of PpIX.Upon light exposure,PPTN generated ROS,not only directly damaging cancer cells,but also trigger the breakage of thioketal bond to accelerate simultaneous release of NLG919.Therefore,PPTN potentially act as a promising ROS/photo dual-responsive carrier-free prodrug delivery system for controllable drug release and specific tumor therapy.Moreover,PPTN induced simultaneous PDT-triggered immunogenic cell death(ICD)effect and specific IDO blockade to boost immune response,exhibiting potent suppression efficacy against primary and distant tumors.Overall,with the superiorities of easily controllable preparation procedures,synchronous drug delivery and ROS/photo dual-responsiveness,such a prodrug unimolecular micelle may represent a promising nanoplatform for photoactivated-immunotherapy.
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.
