Take-home message:This Chinese expert consensus focuses on the hematoporphyrin derivative (HpD) photodynamic therapy(PDT) in cervical high-grade squamous intraepithelial lesion (HSIL).It aims to provide systematic gui...Take-home message:This Chinese expert consensus focuses on the hematoporphyrin derivative (HpD) photodynamic therapy(PDT) in cervical high-grade squamous intraepithelial lesion (HSIL).It aims to provide systematic guidance for gynaecologists,oncologists,nursing professionals and PDT practitioners at all levels in the clinical application of HpD-PDT for the treatment of cervical HSIL.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
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
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
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
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
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)employs lasers to activate photosensitizers,generating reactive oxygen species(ROS)for tumor cell destruction.However,the extremely short half-life of ROS and limited diffusion range restrict ...Photodynamic therapy(PDT)employs lasers to activate photosensitizers,generating reactive oxygen species(ROS)for tumor cell destruction.However,the extremely short half-life of ROS and limited diffusion range restrict PDT’s therapeutic efficiency.Recent studies have shown that lysosome-targeted PDT can directly disrupt the“explosive depot”of tumor cells by triggering the release of abundant hydrolases from lysosomes.Nevertheless,existing lysosometargeted strategies rely predominantly on a single protonation mechanism,resulting in low targeted efficiency.To enhance lysosome-targeted bursting,this study adopted a dual-mode recognition strategy,combining“hydrophobic interactionaided fusion”with“charge-directed anchoring”.Specifically,pyropheophorbide-a(PPa)was employed as a model photosensitizer and covalently conjugated with alkyl tertiary amines of varying chain lengths(C1,C4,C8,and C12),yielding lysosome-targeted bursting photosensitizers(PPa1,PPa4,PPa8,and PPa12).Self-assembled nanoparticles(LPPa NPs)were then prepared to facilitate tumor delivery.The objective of this study was to determine the optimal chain length by evaluating the balance among ROS production efficiency,lysosomal targeted capability,and assembly stability of LPPa NPs.Notably,PPa4 NPs demonstrated superior cellular uptake,enhanced ROS generation,and effective lysosometargeted bursting,thereby markedly improving antitumor efficacy.In summary,the dual-mode recognition strategy offered an advanced strategy for enhancing the efficiency of PDT.展开更多
Photodynamic therapy (PDT) is undoubtedly a cutting-edge strategy for precise tumor therapy because of its unprecedented superiorities, such as negligible long-lasting adverse effects, high spatial and temporal select...Photodynamic therapy (PDT) is undoubtedly a cutting-edge strategy for precise tumor therapy because of its unprecedented superiorities, such as negligible long-lasting adverse effects, high spatial and temporal selectivity, and inappreciable drug resistance. While the operation wavelengths of the commonly used photosensitizers (PSs) are located in visible or first near-infrared (NIR-I, 650–900 nm) region. The lights in these regions possess relatively low penetration depth, which makes PDT unsuitable for deep-tissue treatment. Near-infrared-II (NIR-II, 1000–1700 nm) light with high tissue penetration ability can be employed as excitation source for PDT, which provides a promising alternative for precision therapy of deep-seated tumors. However, designing NIR-II activated PSs is in its infancy, and still faces many challenges, such as severe nonradiative relaxation and difficulties in adjusting energy levels. This paper reviews the therapeutic mechanisms of PDT and recent strategies for designing NIR-II activated inorganic PSs. The inorganic NIR-II PSs are classified based on their functions (such as type II PSs, type I PSs, and PSs with specific properties), and their applications for effective and precision deep-tissue treatment are summarized comprehensively. Furthermore, the major issues of applying these PSs in clinical practices are also discussed.展开更多
Bacterial infections pose a significant threat to human health and entail substantial economic losses.Due to the broad-spectrum antibacterial effect and low susceptibility to drug resistance,photodynamic therapy(PDT),...Bacterial infections pose a significant threat to human health and entail substantial economic losses.Due to the broad-spectrum antibacterial effect and low susceptibility to drug resistance,photodynamic therapy(PDT),a nontraditional antibacterial approach,has garnered a lot of attention.In PDT,the selection of photosensitizer(PS)is crucial because it directly affects the efficiency and safety of the treatment.As a versatile fluorophore,the advantages of 4,4-difluoro-4-bora-3a,4a-diaza-s-indacene(BODIPY)used as a PS for antibacterial PDT are mainly reflected in its high quantum yield of singlet oxygen,easy modification,and exceptional photostability.Through strategic chemical modifications of the BODIPY structures,it is possible to enhance their photodynamic antibacterial activity and refine their selectivity for bacterial killing.This review focuses on the application of BODIPY-based PSs for treating bacterial infections.According to the design strategies of photodynamic antibacterial materials incorporating BODIPY,a variety of representative therapeutic agents having emerged in recent years are classified and discussed,aiming to offer insights for future research and development in this field.展开更多
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 widely used in cancer treatment because of its noninvasiveness and minimal side effects.However,low therapeutic efficiency and the challenge of treatment visualization limit its development...Photodynamic therapy(PDT)is widely used in cancer treatment because of its noninvasiveness and minimal side effects.However,low therapeutic efficiency and the challenge of treatment visualization limit its development.Herein,we constructed a simple yet efficient lanthanide-doped theranostic nanoplatform termed as LiLuF_(4):Yb,Er,Ce@LiYF_(4)@LiLuF_(4):Nd-chlorine 6(TNPs-Ce6)that enables real-time monitoring of the therapeutic effects of PDT.Upon orthogonal excitation by near-infrared(NIR)light,the Nd^(3+)-doped TNPs activated the triplets of Ce6 photosensitizers via a direct lanthanide-triplet energy transfer process,which allowed to directly active the low-lying triplet state of the photosensitizer without undergoing singlet-triplet intersystem crossing(ISC)process,thereby significantly enhancing the efficiency of the photodynamic process.Meanwhile,the incorporation of Er^(3+)ions within the core endowed the nanoplatform with NIR-Ⅱb imaging capabilities,allowing convenient real-time monitoring of the photodynamic treatment process.Characterization tests revealed that the TNPs-Ce6 nanoplatform,exhibiting an NIR quantum yield of 21.7%at an ultralow excitation power density of 0.1 W cm^(-2),provides a real-time imaging resolution as low as75μm in the NIR-Ⅱb range and achieves a tumor suppression rate of 94%.Therefore,this highly efficient theranostic nanoplatform,with real-time treatment monitoring capability,demonstrates significant potential in cancer therapy.展开更多
Magnesium implants have received widespread attention in orthopaedic surgery.However,the mechanical degradation and concurrent inflammation caused by the rapid corrosion of Mg limits their applications.In this study,a...Magnesium implants have received widespread attention in orthopaedic surgery.However,the mechanical degradation and concurrent inflammation caused by the rapid corrosion of Mg limits their applications.In this study,a kind of unique core-shell heterojunction CuS@PPy nanostructures was synthesized and then incorporated in polycaprolactone(PCL)to construct an intelligent coating(CuS@PPy/PCL)on micro-arc-oxidized Mg implants.The PCL-based coating can realize near-infrared(NIR)-driven antibacterial and controllable Mg dissolution according to different bone healing stages.At the beginning of bone remodelling,the coating exhibits promising antibacterial properties with 99.67%and 99.17%efficacy against S.aureus and E.coli,respectively,thanks to the singlet oxygen(^(1)O_(2))and alkoxyl radicals(RO·)generated by the photodynamic effect of CuS@PPy heterojunction under low-power NIR light(1.5 W/cm^(2)).In the bone reparative stage,the PCL-based coating can maintain high corrosion resistance to meet the mechanical requirements of Mg implants in human body fluid.However,after the complete rehabilitation of bones,through a high-power(2 W/cm^(2))NIR light,the PCL-based coating changed from an elastic to a viscous flow state(44.7℃)under the photothermal effects of CuS@PPy,leading to quick degradation of the PCL-based coating and following accelerating dissolution of the Mg implant(avoiding secondary surgery).Hopefully,this NIR-responsive coating may provide an innovative method for the antibacterial and controllable dissolution of Mg implants.展开更多
The inherent low immunogenicity and immunosuppressive metabolism of solid tumors significantly attenuate the immunotherapeutic effect and restrict the immune response.In this work,an endoplasmic reticulum(ER)targeting...The inherent low immunogenicity and immunosuppressive metabolism of solid tumors significantly attenuate the immunotherapeutic effect and restrict the immune response.In this work,an endoplasmic reticulum(ER)targeting photodynamic oxidizer(designated as PhotoOx)is fabricated to boost the antitumor immunity by integrating photodynamic therapy(PDT)induced immunogenic cell death(ICD)with indoleamine 2,3-dioxygenase 1(IDO1)inhibition.Among which,an ER targeting photosensitizer-peptide conjugate called PhotoPe is rationally designed for optimal functionality and amphiphilicity,which could self-assemble into nano-micelles co-delivering chlorin e6 and NLG919.PhotoOx exhibits a good stability to enable ER targeting drug delivery,which could induce ER rupture to intensify PDT induced ICD and release damage associated molecular patterns(DAMPs).Furthermore,PhotoOx could effectively initiate immunological cascades,leading to the suppression of regulatory T cells(Tregs)and activation of CD8^(+)T cells when combines with IDO inhibition.Furthermore,the multi-synergistic effects of PhotoOx activate a robust systemic anti-tumor immune response,resulting in the eradication of lung and liver metastases.Such a medication strategy might inspire the rational design of biomedicine for precise drug delivery,which also provides a sophisticated mechanism for addressing the challenges of solid tumor treatment.展开更多
Photodynamic therapy(PDT)presents a promising avenue in cancer treatment.Erlotinib,an FDAapproved anticancer drug targeting epidermal growth factor receptor(EGFR),has shown effectiveness in normalizing tumor vasculatu...Photodynamic therapy(PDT)presents a promising avenue in cancer treatment.Erlotinib,an FDAapproved anticancer drug targeting epidermal growth factor receptor(EGFR),has shown effectiveness in normalizing tumor vasculature across various tumors,thereby promoting tumor oxygenation and facilitating PDT.In this work,erlotinib was conjugated with a near-infrared(NIR)photosensitizer,benzo[a]phenoselenazinium,yielding three EGFR-targeted PDT agents(NBSe-n C-Er).These newly synthesized photosensitizers demonstrate specificity in binding to EGFR,thereby enhancing their accumulation in cancer cells and tumors,and consequently improving the efficiency of both PDT and chemotherapy.Additionally,the NIR fluorescence emitted by the photosensitizer allows for imaging-guided therapy,offering a non-invasive means of monitoring treatment progress.The distinctive properties of the three-inone photosensitizer render it an ideal candidate for precise tumor treatment,overcoming the limitations of conventional therapies.展开更多
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
Photodynamic therapy(PDT)is an emerging minimally invasive therapeutic modality that relies on the activation of a photosensitizing agent by light of a specific wavelength in the presence of molecular oxygen,leading t...Photodynamic therapy(PDT)is an emerging minimally invasive therapeutic modality that relies on the activation of a photosensitizing agent by light of a specific wavelength in the presence of molecular oxygen,leading to the generation of reactive oxygen species(ROS).This mechanism facilitates selective cytotoxic effects within pathological tissues and has demonstrated therapeutic potential across diverse disease contexts.However,the broader clinical applications remain limited by photosensitizer selectivity,shallow light penetration,and the risk of off-target cytotoxicity.Recent advancements in PDT have focused on the development of next-generation photosensitizers,the integration of nanotechnology for enhanced delivery and targeting,and the strategic combination of PDT with complementary therapeutic approaches.Experimental animal models play a crucial role in validating the efficacy and safety of PDT,optimizing its therapeutic parameters,and determining its mechanisms of action.This review provides a comprehensive overview of PDT applications in various disease models,including oncological,infectious,and nonconventional indications.Special emphasis is placed on the importance of large animal models in PDT research,such as rabbits,pigs,dogs,and non-human primates,which provide experimental platforms that more closely resemble human physiological and pathological states.The use of these models for understanding the mechanisms of PDT,optimizing therapeutic regimens,and evaluating clinical outcomes is also discussed.This review aims to inform future directions in PDT research and emphasizes the importance of selecting appropriate preclinical animal models to facilitate successful clinical translation.展开更多
An increasing number of studies have focused on depleting lactate and modulating the tumor’s lactic microenvironment to interfere with tumor progression,particularly in breast cancer.Lactate accumulation in tumors co...An increasing number of studies have focused on depleting lactate and modulating the tumor’s lactic microenvironment to interfere with tumor progression,particularly in breast cancer.Lactate accumulation in tumors contributes to a highly acidic microenvironment that promotes cancer cell survival and resistance to therapies.However,existing lactate depletion agents,primarily enzymes and macromolecules,fall short of clinical applications due to poor stability and their ability to only perform solitary lactate depletion without interfering with the transport process.Consequently,the development of stable molecules that deplete lactate and interfere with lactate transport is critically needed.Therefore,in this study,chlorin e6(Ce6)-gadolinium chloride(GdCl_(3))-flavin adenine dinucleotide(FAD)/tamoxifen(TAM)molecular chelates were prepared.The chelates fully interfered with lactate transport,depleted lactate in the tumor microenvironment,mitigated photodynamic therapy resistance,and realized synergistic photodynamic-hormonal therapy.FAD has promising capabilities in regulating lactate levels and mitigating acidic microenvironments.However,a strategy for depleting lactate by chelating the coenzyme FAD to form nanoparticles has not yet been reported.Tamoxifen disrupts tumor development and interferes with lactate transport by binding to estrogen receptor and inhibiting the expression of monocarboxylate transporter.In addition,coupling with Gd^(3+)increased the solubility of Ce6,thereby improving the photodynamic therapy effectiveness.This innovative strategy improves therapeutic efficacy and offers a promising approach for breast cancer treatment.展开更多
The efficacy of photodynamic therapy(PDT)for breast tumors is hindered by challenges such as inadequate tumor targeting,limited treatment depth,and strong oxygen dependence.Herein,a promising photosensitizer VP-B was ...The efficacy of photodynamic therapy(PDT)for breast tumors is hindered by challenges such as inadequate tumor targeting,limited treatment depth,and strong oxygen dependence.Herein,a promising photosensitizer VP-B was developed to simultaneously address all the aforementioned issues for the treatment of hypoxic deep-seated breast tumors.The biotinylated photosensitizer VP-B not only exhibited precise targeting towards breast tumor tissue,but also efficiently triggered the generation of abundant1O2and O2-·under 690 nm red light irradiation.Indeed,the red light penetration ability enabled VP-B to achieve successful application in a mouse orthotopic breast tumor model.After intravenous administration,VP-B can selectively target tumor tissues and significantly inhibit the growth of hypoxic deep-seated tumors.Therefore,this new typeⅠ&Ⅱphotosensitizer could boost fluorescence-guided photodynamic therapy of other hypoxic solid tumors.展开更多
基金supported by the National Key R&D Program of China (2024YFC2707503)Sanming Project of Medicine in Shenzhen (SZSM202011016)+2 种基金Shenzhen Public Platform for Preservation of Fertility and Reproduction (XMHT20220104049)Shenzhen Key Medical Discipline Construction Fund (SZXK027)the specific research fund of The Innovation Platform for Academicians of Hainan Province (YSPTZX202202)。
文摘Take-home message:This Chinese expert consensus focuses on the hematoporphyrin derivative (HpD) photodynamic therapy(PDT) in cervical high-grade squamous intraepithelial lesion (HSIL).It aims to provide systematic guidance for gynaecologists,oncologists,nursing professionals and PDT practitioners at all levels in the clinical application of HpD-PDT for the treatment of cervical HSIL.
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.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 Major Science and Technology Special Projects in Henan Province(No.221100310100)co-construction Project of Henan Medical Science and Technology(LHGJ20230286).
文摘Cerenkov radiation(CR)can serve as a source of internal light to overcome the limited tissue penetration of external light in conventional photodynamic therapy(PDT).However,insufficient luminescence intensity hinders the clinical application of CR-PDT.Here,we developed a glutathione-responsive biomimetic nanoplatform by fusing cancer cell membranes and liposomes loaded with photosensitizer hematoporphyrin monomethyl ether(HMME)and a radiation energy amplifier Eu^(3+),named HMME-Eu@LEV.Colloidal Eu^(3+)convertsγ-radiation and CR from radioisotopes into fluorescence to enhance antitumor effects.Sequential administration ensures co-localization of HMME-Eu@LEV and radiopharmaceutical^(18)F-fluorodeoxyglucose(FDG)at the tumor site,triggering enhanced CR-PDT and immunogenic cell death.Our observations indicated that luminescence resonance energy transfer between Eu^(3+)and HMME was efficient,and Cerenkov luminescence from Eu@LEV+FDG was approximately 5.6-fold higher in intensity than that from FDG alone.As a result,abundant ROS were generated,and macrophages in the tumor microenvironment were polarized from M2 to M1.In addition,the immunosuppressive tumor microenvironment could be reversed by promoting the maturation of dendritic cells and infiltration of cytotoxic T lymphocytes.The activated immune system effectively inhibited the growth of primary tumors and spread of distant metastases.Our work demonstrates the feasibility of CR-PDT without an external light source and the critical role of nanomaterials in personalized medicine.
基金supported by the National Natural Science Foundation of China(Nos.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 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 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National Natural Science Foundation of China(No.82204318)Liaoning Revitalization Talents Program(Nos.XLYC22202019,and XLYC2203083)+3 种基金Natural Science Foundation of Henan,Guided Youth Science Fund Project(No.242300420424)Henan Eye Hospital Basic Science Research Program(No.25JCQN004)Key research and development program of Liaoning Province(No.2024JH2/102500061)Youth innovation team of Liaoning Province Department of Education(No.LJ222410163049).
文摘Photodynamic therapy(PDT)employs lasers to activate photosensitizers,generating reactive oxygen species(ROS)for tumor cell destruction.However,the extremely short half-life of ROS and limited diffusion range restrict PDT’s therapeutic efficiency.Recent studies have shown that lysosome-targeted PDT can directly disrupt the“explosive depot”of tumor cells by triggering the release of abundant hydrolases from lysosomes.Nevertheless,existing lysosometargeted strategies rely predominantly on a single protonation mechanism,resulting in low targeted efficiency.To enhance lysosome-targeted bursting,this study adopted a dual-mode recognition strategy,combining“hydrophobic interactionaided fusion”with“charge-directed anchoring”.Specifically,pyropheophorbide-a(PPa)was employed as a model photosensitizer and covalently conjugated with alkyl tertiary amines of varying chain lengths(C1,C4,C8,and C12),yielding lysosome-targeted bursting photosensitizers(PPa1,PPa4,PPa8,and PPa12).Self-assembled nanoparticles(LPPa NPs)were then prepared to facilitate tumor delivery.The objective of this study was to determine the optimal chain length by evaluating the balance among ROS production efficiency,lysosomal targeted capability,and assembly stability of LPPa NPs.Notably,PPa4 NPs demonstrated superior cellular uptake,enhanced ROS generation,and effective lysosometargeted bursting,thereby markedly improving antitumor efficacy.In summary,the dual-mode recognition strategy offered an advanced strategy for enhancing the efficiency of PDT.
基金supported by the National Natural Science Foundation of China(Nos.22175098,52373142)the Jiangsu Planned Projects for Postdoctoral Research Funds(No.2021K114B)the Huali Talents Program of Nanjing University of Posts and Telecommunications,the Postgraduate Research&Practice Innovation Program of Jiangsu Province(No.KYCX23_0984)。
文摘Photodynamic therapy (PDT) is undoubtedly a cutting-edge strategy for precise tumor therapy because of its unprecedented superiorities, such as negligible long-lasting adverse effects, high spatial and temporal selectivity, and inappreciable drug resistance. While the operation wavelengths of the commonly used photosensitizers (PSs) are located in visible or first near-infrared (NIR-I, 650–900 nm) region. The lights in these regions possess relatively low penetration depth, which makes PDT unsuitable for deep-tissue treatment. Near-infrared-II (NIR-II, 1000–1700 nm) light with high tissue penetration ability can be employed as excitation source for PDT, which provides a promising alternative for precision therapy of deep-seated tumors. However, designing NIR-II activated PSs is in its infancy, and still faces many challenges, such as severe nonradiative relaxation and difficulties in adjusting energy levels. This paper reviews the therapeutic mechanisms of PDT and recent strategies for designing NIR-II activated inorganic PSs. The inorganic NIR-II PSs are classified based on their functions (such as type II PSs, type I PSs, and PSs with specific properties), and their applications for effective and precision deep-tissue treatment are summarized comprehensively. Furthermore, the major issues of applying these PSs in clinical practices are also discussed.
文摘Bacterial infections pose a significant threat to human health and entail substantial economic losses.Due to the broad-spectrum antibacterial effect and low susceptibility to drug resistance,photodynamic therapy(PDT),a nontraditional antibacterial approach,has garnered a lot of attention.In PDT,the selection of photosensitizer(PS)is crucial because it directly affects the efficiency and safety of the treatment.As a versatile fluorophore,the advantages of 4,4-difluoro-4-bora-3a,4a-diaza-s-indacene(BODIPY)used as a PS for antibacterial PDT are mainly reflected in its high quantum yield of singlet oxygen,easy modification,and exceptional photostability.Through strategic chemical modifications of the BODIPY structures,it is possible to enhance their photodynamic antibacterial activity and refine their selectivity for bacterial killing.This review focuses on the application of BODIPY-based PSs for treating bacterial infections.According to the design strategies of photodynamic antibacterial materials incorporating BODIPY,a variety of representative therapeutic agents having emerged in recent years are classified and discussed,aiming to offer insights for future research and development in this field.
基金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 Major Research plan of the National Natural Science Foundation of China(No.92361202)National Natural Science Foundation of China(No.12204481)+3 种基金Fund of Fujian Science&Technology Innovation Laboratory for Optoelectronic Information(No.2020ZZ114)Natural Science Foundation of Fujian Province(Nos.2022J05102 and 2024J09062)National Key Research and Development Program of China(Nos.2022YFB3503700 and 2023YFF0713605)Self-deployment Project Research Program of Haixi Institutes,Chinese Academy of Sciences(No.CXZX-2022-GS01)
文摘Photodynamic therapy(PDT)is widely used in cancer treatment because of its noninvasiveness and minimal side effects.However,low therapeutic efficiency and the challenge of treatment visualization limit its development.Herein,we constructed a simple yet efficient lanthanide-doped theranostic nanoplatform termed as LiLuF_(4):Yb,Er,Ce@LiYF_(4)@LiLuF_(4):Nd-chlorine 6(TNPs-Ce6)that enables real-time monitoring of the therapeutic effects of PDT.Upon orthogonal excitation by near-infrared(NIR)light,the Nd^(3+)-doped TNPs activated the triplets of Ce6 photosensitizers via a direct lanthanide-triplet energy transfer process,which allowed to directly active the low-lying triplet state of the photosensitizer without undergoing singlet-triplet intersystem crossing(ISC)process,thereby significantly enhancing the efficiency of the photodynamic process.Meanwhile,the incorporation of Er^(3+)ions within the core endowed the nanoplatform with NIR-Ⅱb imaging capabilities,allowing convenient real-time monitoring of the photodynamic treatment process.Characterization tests revealed that the TNPs-Ce6 nanoplatform,exhibiting an NIR quantum yield of 21.7%at an ultralow excitation power density of 0.1 W cm^(-2),provides a real-time imaging resolution as low as75μm in the NIR-Ⅱb range and achieves a tumor suppression rate of 94%.Therefore,this highly efficient theranostic nanoplatform,with real-time treatment monitoring capability,demonstrates significant potential in cancer therapy.
基金support to this work:the National Natural Science Foundation of China(grant No.50971064,No.51361004)the Innovative Foundation of HUST(grant 2017KFYXJJ164).
文摘Magnesium implants have received widespread attention in orthopaedic surgery.However,the mechanical degradation and concurrent inflammation caused by the rapid corrosion of Mg limits their applications.In this study,a kind of unique core-shell heterojunction CuS@PPy nanostructures was synthesized and then incorporated in polycaprolactone(PCL)to construct an intelligent coating(CuS@PPy/PCL)on micro-arc-oxidized Mg implants.The PCL-based coating can realize near-infrared(NIR)-driven antibacterial and controllable Mg dissolution according to different bone healing stages.At the beginning of bone remodelling,the coating exhibits promising antibacterial properties with 99.67%and 99.17%efficacy against S.aureus and E.coli,respectively,thanks to the singlet oxygen(^(1)O_(2))and alkoxyl radicals(RO·)generated by the photodynamic effect of CuS@PPy heterojunction under low-power NIR light(1.5 W/cm^(2)).In the bone reparative stage,the PCL-based coating can maintain high corrosion resistance to meet the mechanical requirements of Mg implants in human body fluid.However,after the complete rehabilitation of bones,through a high-power(2 W/cm^(2))NIR light,the PCL-based coating changed from an elastic to a viscous flow state(44.7℃)under the photothermal effects of CuS@PPy,leading to quick degradation of the PCL-based coating and following accelerating dissolution of the Mg implant(avoiding secondary surgery).Hopefully,this NIR-responsive coating may provide an innovative method for the antibacterial and controllable dissolution of Mg implants.
基金supported by the National Natural Science Foundation of China(No.32371394)the National Key R&D Program of China(No.2021YFD1800600)+3 种基金the Special Projects in Key Areas of Colleges and Universities in Guangdong Province(No.2022ZDZX2046)the Open Project of State Key Laboratory of Respiratory Disease(No.SKLRD-OP-202502)the Postdoctoral Fellowship Program of CPSF(No.GZC20230619)Postdoctoral startup funding of Guangzhou Medical University(No.Q0301–130)。
文摘The inherent low immunogenicity and immunosuppressive metabolism of solid tumors significantly attenuate the immunotherapeutic effect and restrict the immune response.In this work,an endoplasmic reticulum(ER)targeting photodynamic oxidizer(designated as PhotoOx)is fabricated to boost the antitumor immunity by integrating photodynamic therapy(PDT)induced immunogenic cell death(ICD)with indoleamine 2,3-dioxygenase 1(IDO1)inhibition.Among which,an ER targeting photosensitizer-peptide conjugate called PhotoPe is rationally designed for optimal functionality and amphiphilicity,which could self-assemble into nano-micelles co-delivering chlorin e6 and NLG919.PhotoOx exhibits a good stability to enable ER targeting drug delivery,which could induce ER rupture to intensify PDT induced ICD and release damage associated molecular patterns(DAMPs).Furthermore,PhotoOx could effectively initiate immunological cascades,leading to the suppression of regulatory T cells(Tregs)and activation of CD8^(+)T cells when combines with IDO inhibition.Furthermore,the multi-synergistic effects of PhotoOx activate a robust systemic anti-tumor immune response,resulting in the eradication of lung and liver metastases.Such a medication strategy might inspire the rational design of biomedicine for precise drug delivery,which also provides a sophisticated mechanism for addressing the challenges of solid tumor treatment.
基金supported by the National Natural Science Foundation of China(Nos.22278447 and 22178395)State Key Laboratory of Fine Chemicals(No.KF2109)State Key Laboratory of Chemo/Biosensing and Chemometrics(No.20230768)。
文摘Photodynamic therapy(PDT)presents a promising avenue in cancer treatment.Erlotinib,an FDAapproved anticancer drug targeting epidermal growth factor receptor(EGFR),has shown effectiveness in normalizing tumor vasculature across various tumors,thereby promoting tumor oxygenation and facilitating PDT.In this work,erlotinib was conjugated with a near-infrared(NIR)photosensitizer,benzo[a]phenoselenazinium,yielding three EGFR-targeted PDT agents(NBSe-n C-Er).These newly synthesized photosensitizers demonstrate specificity in binding to EGFR,thereby enhancing their accumulation in cancer cells and tumors,and consequently improving the efficiency of both PDT and chemotherapy.Additionally,the NIR fluorescence emitted by the photosensitizer allows for imaging-guided therapy,offering a non-invasive means of monitoring treatment progress.The distinctive properties of the three-inone photosensitizer render it an ideal candidate for precise tumor treatment,overcoming the limitations of conventional therapies.
基金supported by the National Natural Science Foundation of China(22378126)National Key Research and Development Program of the International scientific and technological innovation cooperation project among governments(2021YFE0100400)Shanghai Science and Technology Innovation Action Plan(22501100500).
文摘Integrating multiple modalities of cancer therapies for synergistic and enhanced therapeutic efficacy remains challenging.Herein,flash nanoprecipitation(FNP),a kinetically driven process,was employed to expedite the coordination reaction time required for nano-encapsulate components with completely opposite physiochemical properties including sorafenib(SRF),hemoglobin(Hb),chlorin e6(Ce6),and indocyanine green(ICG)into a multi-component HSCI nanomedicine.Hydrophilic components Hb and ICG interact to form hydrophobic ICG-Hb complexes under electrostatic and hydrophobic interactions.This process facilitates the characteristic time of nucleation(τ_(nucleation))to match the characteristic mixing time(τ_(mix))of the FNP process,resulting in the formulation of kinetically stable nanomedicine,overcoming the long equilibrium times and instability issues associated with thermodynamic assembly.Importantly,pH-responsive structure is also easily but effectively integrated in nanomedicine during this kinetically driven formulation to manipulate its structures.In the acidic tumor microenvironment(TME),the pH-stimulated morphology transformation of HSCI nanomedicine boosts its reactive oxygen species(ROS)generation efficiency and photothermal efficacy,endowing it with better antitumor suppression.In vitro and in vivo experiments reveal that the HSCI nanomedicine offers a synergistic therapeutic effect and stronger tumor suppression compared with single therapies.These results open a new window for developing strategies for multimodal combinatory cancer therapies.
基金supported by the China Postdoctoral Science Foundation(2024M751098,2024M761134)Jilin Province Development and Reform Commission Program(ZKJCFGW2023015)+1 种基金Wenzhou Science&Technology Bureau Basic Public Welfare Research Program(Y20240006)Jilin University Young Teachers and Students Cross-disciplinary Training Project(2023-JCXK-08)。
文摘Photodynamic therapy(PDT)is an emerging minimally invasive therapeutic modality that relies on the activation of a photosensitizing agent by light of a specific wavelength in the presence of molecular oxygen,leading to the generation of reactive oxygen species(ROS).This mechanism facilitates selective cytotoxic effects within pathological tissues and has demonstrated therapeutic potential across diverse disease contexts.However,the broader clinical applications remain limited by photosensitizer selectivity,shallow light penetration,and the risk of off-target cytotoxicity.Recent advancements in PDT have focused on the development of next-generation photosensitizers,the integration of nanotechnology for enhanced delivery and targeting,and the strategic combination of PDT with complementary therapeutic approaches.Experimental animal models play a crucial role in validating the efficacy and safety of PDT,optimizing its therapeutic parameters,and determining its mechanisms of action.This review provides a comprehensive overview of PDT applications in various disease models,including oncological,infectious,and nonconventional indications.Special emphasis is placed on the importance of large animal models in PDT research,such as rabbits,pigs,dogs,and non-human primates,which provide experimental platforms that more closely resemble human physiological and pathological states.The use of these models for understanding the mechanisms of PDT,optimizing therapeutic regimens,and evaluating clinical outcomes is also discussed.This review aims to inform future directions in PDT research and emphasizes the importance of selecting appropriate preclinical animal models to facilitate successful clinical translation.
基金supported by the National Natural Science Foundation of China(No.82373206)Zhejiang Provincial Natural Science Foundation of China under Grant No LHDMZ24H300002National Key Research and Development Program of China(No.2022YFE0107800,2023YFA1008603).
文摘An increasing number of studies have focused on depleting lactate and modulating the tumor’s lactic microenvironment to interfere with tumor progression,particularly in breast cancer.Lactate accumulation in tumors contributes to a highly acidic microenvironment that promotes cancer cell survival and resistance to therapies.However,existing lactate depletion agents,primarily enzymes and macromolecules,fall short of clinical applications due to poor stability and their ability to only perform solitary lactate depletion without interfering with the transport process.Consequently,the development of stable molecules that deplete lactate and interfere with lactate transport is critically needed.Therefore,in this study,chlorin e6(Ce6)-gadolinium chloride(GdCl_(3))-flavin adenine dinucleotide(FAD)/tamoxifen(TAM)molecular chelates were prepared.The chelates fully interfered with lactate transport,depleted lactate in the tumor microenvironment,mitigated photodynamic therapy resistance,and realized synergistic photodynamic-hormonal therapy.FAD has promising capabilities in regulating lactate levels and mitigating acidic microenvironments.However,a strategy for depleting lactate by chelating the coenzyme FAD to form nanoparticles has not yet been reported.Tamoxifen disrupts tumor development and interferes with lactate transport by binding to estrogen receptor and inhibiting the expression of monocarboxylate transporter.In addition,coupling with Gd^(3+)increased the solubility of Ce6,thereby improving the photodynamic therapy effectiveness.This innovative strategy improves therapeutic efficacy and offers a promising approach for breast cancer treatment.
基金supported financially by the National Key Research and Development Program of China(No.2023YFC3403000)the National Natural Science Foundation of China(No.22378231)the Guangdong Basic and Applied Basic Research Foundation(No.2024A1515012493)。
文摘The efficacy of photodynamic therapy(PDT)for breast tumors is hindered by challenges such as inadequate tumor targeting,limited treatment depth,and strong oxygen dependence.Herein,a promising photosensitizer VP-B was developed to simultaneously address all the aforementioned issues for the treatment of hypoxic deep-seated breast tumors.The biotinylated photosensitizer VP-B not only exhibited precise targeting towards breast tumor tissue,but also efficiently triggered the generation of abundant1O2and O2-·under 690 nm red light irradiation.Indeed,the red light penetration ability enabled VP-B to achieve successful application in a mouse orthotopic breast tumor model.After intravenous administration,VP-B can selectively target tumor tissues and significantly inhibit the growth of hypoxic deep-seated tumors.Therefore,this new typeⅠ&Ⅱphotosensitizer could boost fluorescence-guided photodynamic therapy of other hypoxic solid tumors.
